Trond Halstensen - Academia.edu (original) (raw)
Papers by Trond Halstensen
Immunology
The specialized M cells in the follicle-associated epithelium (FAE) of Peyer's patches (PP) repre... more The specialized M cells in the follicle-associated epithelium (FAE) of Peyer's patches (PP) represent an intimate interphase between luminal antigens and gut-associated lymphoid tissue (GALT). M cells form pockets that contain clusters of leucocytes probably involved in the first encounter with antigens from the gut lumen. Three-colour immunofluorescence in situ phenotyping of these leucocytes in humans revealed about equal numbers of B (CD19/20+) and T (CD3 +) lymphocytes, the latter mainly CD4+ (median 73%, range 40-90%), but relatively few macrophages (CD68 +). Most B cells (90%) were positive for surface IgM (sIgM) and often co-expressed sIgD (median 34%, range 6-60%). Occasional B cells (median 2%) did not express CD45RA (range 0-15%) and 13% virtually lacked HLA-DR (range 0-40%). Some B and T lymphocytes expressed the nuclear proliferation marker Ki-67 (range 1-10%). The M-cell pockets also contained occasional cells with cytoplasmic IgA or IgM. These sites thus contained a heterogeneous B-cell population with features of both follicular mantle (sIgD+ sIgM+) and marginal zone (sIgD-sIgM +) B lymphocytes. Adjacent T lymphocytes were generally of the memory phenotype (CD45RO+). Our findings suggest that the M-cell-associated B lymphocytes represent local extensions of B-cell follicles towards the gut lumen, developed topically to facilitate antigen presentation and diversification of mucosal immune responses. FAE of rats, mice and rabbits6,10,11 contains more B and T
Advances in Experimental Medicine and Biology
In conclusion, the "M(r) 40kD" antigen is expressed on the apical face of colon... more In conclusion, the "M(r) 40kD" antigen is expressed on the apical face of colonic enterocytes often in spatial relation to immune complexes in active UC, apparently targeting an IgG1-mediated autoimmune attack. Thus, our findings support the notion that an autoimmune response to the "M(r) 40kD" antigen, with local production of specific IgG1, is a possible immunopathological mechanism(s) in UC.
Advances in Experimental Medicine and Biology
In conclusion, it appears that gluten induces a non-proliferative activation of CD4+ lamina propr... more In conclusion, it appears that gluten induces a non-proliferative activation of CD4+ lamina propria T cells, but a proliferative activation in the TCR alpha/beta +CD8+ and TCR gamma/delta + IEL subsets. Although the increased density of TCR alpha/beta +CD8+ and TCR gamma/delta + IEL in the coeliac lesion may be secondary to T cell mediated immune activation in the lamina propria, a direct and primary antigen-driven proliferation of IEL (perhaps CD1-dependent29) cannot be excluded.
Advances in Experimental Medicine and Biology
American Journal Of Pathology
In mice, integrin a4f87 is the main receptor used by lymphocytes that home to the Peyer's patches... more In mice, integrin a4f87 is the main receptor used by lymphocytes that home to the Peyer's patches, although L-selectin contributes to the initial interaction with high endothelial venules. Less is known about the expression and function of these adbesion molecules in humans. The distribution of L-selectin and a4f37 on various B-and T-ceU subsets was examined in human Peyer's patches (n = 8) and appendix (n = 4), coUectively caUed gut-associated lymphoid tissue. Multicolor immunophenotyping was performed on cryosections, and dispersed ceUs were examined by flow cytometry. In cryosections, CD45RA + T ceUs around and within interfoUicular high endothelial venules, as weUl as surface (s)IgD' B lymphocytes in the follicle mantles, often expressed abundant L-selectin but only intermediate levels of ac4137. CD45RO+ T ceUs and sIgD-B ceUs expressed higher levels of ac4187 and were often located near putative efferent lymphatics; only a smaU fraction (<20%) of such memory ceUs expressed L-selectin. By flow cytometry, considerably more T than B lymphocytes co-expressed L-selectin and a4137 (40% versus 25% and 67% versus 39%, respectively). In samples with many L-selectin+ ceUs (>30%), more ofthese lymphocytes co-expressed a4j37 than in samples withfew L-selectin+ ceUs. Because L-selectin and a4137 were co-expressed on lymphocytes located near high endothelial venules, and because such co-expression was relatively common when many L-selectin + ceUs werepresent, both ofthese molecules migbt participate in boming to human gut-associated lymphoid tissue. Such homing is probably most pronounced for T lymphocytes that were found to express L-selectin and ac4137 more often than B lymphocytes. The selective and relatively high expression of a4137 on memory ceUs located near efferent lymphatics indicated a different migratory capacity; after exitfrom gutassociated lymphoid tissue, such stimulated cells might bome mainly to mucosal effector sites. (Am J Pathol 1997, 150:187-199) Gut-associated lymphoid tissue (GALT) comprises Peyer's patches (PPs), appendix, and solitary lymphoid follicles scattered throughout the intestinal mucosa. B and T lymphocytes are primed against intestinal antigens in GALT and are subsequently seeded as memory or effector cells to distant mucosal effector sites, especially the gut lamina propria. Such homing is well established for IgA preursor B cells1 and to some extent also for T cells.2'3 Cytokines or other factors in GALT and mesenteric lymph nodes modulate the expression of surface molecules so that the memory lymphocytes and blasts adhere to endothelial cells of venules in mucosal effector tissues and emigrate there.4 Distinct pairs of such receptors and endothelial ligands (addressins) co-
Scandinavian Journal of Immunology
A revived interest in intraepithelial lymphocytes (IEL) has been elicited by several recent repor... more A revived interest in intraepithelial lymphocytes (IEL) has been elicited by several recent reports suggesting that murine and avian intestinal epithelium contains mainly CD3+CD8+ cells expressing the gamma/delta T-cell receptor (TcR) for antigen; this contrasts with systemically distributed T cells which preferentially employ the TcR alpha/beta. An anatomical dichotomy in the distribution of these two T-cell lineages has hence been proposed. Here we report that this concept does not hold true in man. In situ studies with monoclonal TcR-framework antibodies showed that most (70-90%) human intestinal IEL (which are mainly CD3+CD8+) expressed TcR alpha/beta. Moreover, almost half of the intraepithelial CD3+ cells were positive for the smallest (180 kDa) CD45 molecule (UCHL1); this probably reflected that they are antigen-primed and thus represent traditional CD3+CD8+ alpha/beta+ memory T cells.
Scandinavian Journal of Immunology
Halstensen, TS. Scott, H. & Brandtzaeg. P. Inlraepilhelial T Cells ol" the TcRv/.i'... more Halstensen, TS. Scott, H. & Brandtzaeg. P. Inlraepilhelial T Cells ol" the TcRv/.i' CDS and * Phenotypes are Increased in Coeliac Disease. Stand. J. Immunol. 30, 665-672. 1989 Expression of the / I't T-cell receptor (TcR) for aniigen on CD?' intraepiihelial lymphiwytes (lEL) was studied ...
Journal of Experimental Medicine
Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible indivi... more Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA-DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated ...
Advances in Experimental Medicine and Biology
Gastroenterology
Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (I... more Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (IgG) and M (IgM) antibodies to gluten. Intake of dietary gluten may hence induce local complement activation and mucosal damage. Jejunal tissue sections from adult patients with celiac disease were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and the terminal complement complex (TCC). Subepithelial deposition of TCC was observed in 93% of 28 untreated and in 57% of 23 partly treated study subjects. The immunofluorescence staining intensity was well correlated with the serum level of gluten-specific IgG and IgM (but not IgA), the number of mucosal IgG-producing cells, and the degree of villous atrophy. Similar immune deposits were not observed in 5 successfully treated patients with celiac disease, 5 patients with dermatitis herpetiformis without jejunal villous atrophy, and 90% of 21 control patients with histologically normal jejunal mucosa. ...
Immunology
Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha... more Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha/beta or gamma/delta was studied in situ by three-colour immunofluorescence on jejunal tissue sections from 21 patients with coeliac disease and eight controls. CD45RA-TcR alpha/beta+ IEL expressed CD45RO significantly more often (75%) than the preferentially expanded TcR gamma/delta+ counterpart (59%). Triple staining for CD3, CD4/8 and CD45RA or CD45RB revealed that all CD3 + 4 - 8 - IEL (taken to be TcR gamma/delta+) expressed CD45RB and none were CD45RA. CD45RO positivity was of the same magnitude (66%) on the predominating monoclonal antibody delta TCS1-reactive fraction of TcR gamma/delta+ cells as on the remainder of the TcR gamma/delta+ subset. These results suggest that gluten exposition in patients with coeliac disease leads to accumulation of CD45RA-, putative antigen-primed memory cells of both TcR phenotypes. The less marked CD45RO expression within the preferentially expand...
Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxy... more Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and Ll (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myoeardial arterio-venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of Ll increased during CPB from 344+71
Journal of Virology
The proportion of T-cell receptor gamma/delta+ cells and the CD4/CD8 ratio relative to all CD3+ i... more The proportion of T-cell receptor gamma/delta+ cells and the CD4/CD8 ratio relative to all CD3+ intraepithelial lymphocytes (IEL) were determined by immunofluorescence in duodenal mucosa of late-stage (mostly CDC IVC1/D) subjects (n = 21) infected with human immunodeficiency virus type 1 (HIV-1). The gamma/delta fraction (median, 14.2%; range, 1.7 to 59.8%) was increased (P < 0.03) compared with that in HIV- controls (n = 11; median 2.8%; range, 0.3 to 38%). Also, the number of gamma/delta+ IEL per mucosal unit was increased (P < 0.05) in the HIV+ subjects (median, 11.1/U) compared with the controls (3.2/U). Approximately 100% of the gamma/delta+ IEL were CD8-, and most expressed the Vdelta1vJdelta1-encoded epitope (median, 90.9%). The total number of CD3+ IEL tended to be lower than in the controls (67.4 versus 72.9/U). Both the epithelium and the lamina propria contained mainly CD8+ T cells, the median ratios of CD4+ T cells being 1 and 7.6%, respectively. This result accord...
Gastroenterology, 1989
Abbreviations used in this paper: AX, antigen-presenting cell; BALT, bronchus-associated lymphoid... more Abbreviations used in this paper: AX, antigen-presenting cell; BALT, bronchus-associated lymphoid tissue; C, complement; FAE, follicle-associated epithelium; GALT, gut-associated lymphoid tissue; IBD, inflammatory bowel disease; IEL, intraepithelial lymphocyte: IL-Z, interleukin 2; MHC, major histocompatibility complex; pig, polymeric immunoglobulin; pIgA, polymeric (or dimeric) immunoglobulin A; pIgh4, polymeric immunoglobulin M; PP, Peyer's patch: SC, secretory component; SIgA, secretory immunoglobulin A; SIgM, secretory immunoglobulin M
Gut, 1997
It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposit... more It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposition of various activation products of the complement system may contribute to the pathogenesis of chronic gastritis and was therefore studied by immunohistochemistry. Ethanol fixed antrum or body gastric tissue sections from 24 patients infected with H pylori (determined by bacterial immunohistochemistry) and 22 uninfected patients were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and in the terminal complex (TCC). As a control group, biopsy samples from the gastric stump of 23 Billroth II operated patients were studied. Patchy, bright staining for TCC occurred below the surface epithelium and around the glands in H pylori positive and negative gastritis as well as in stump gastritis but seldom in normal mucosa. Activated C3 was present at the apical face of the surface epithelium, significantly more often in the antrum and body from patients...
Advances in experimental medicine and biology, 1995
Bibliotheca nutritio et dieta, 1991
Progress in histochemistry and cytochemistry, 1992
Journal of Oral Pathology & Medicine, 2014
Expression of the stem cell transcription factor SOX2 is often used to imply stemness and poor pr... more Expression of the stem cell transcription factor SOX2 is often used to imply stemness and poor prognosis in cancer. However, its role in oral squamous cell carcinoma (OSCC) is not fully elucidated. Tumour tissues from 62 patients with primary, node negative and non-metastatic OSCCs were used to evaluate SOX2 expression by immunohistochemistry. The results were correlated to clinicopathology, treatment and disease recurrences. The majority of the OSCCs (88%) expressed SOX2. Patients with higher nuclear SOX2 staining intensity in the invasive front compared to the adjacent normal epithelium, had a remarkable longer disease-free period if they received adjuvant post-operative radiotherapy (P = 0.001). This was in particular evident for highly differentiated OSCCs, as none of the high SOX2-expressing tumours reoccurred in contrast to all low SOX2-expressing OSCCs. High nuclear SOX2 expression in the invasive front was associated with dramatic longer disease-free period than low SOX2-expressing carcinomas after post-operative radiotherapy in small OSCCs. The result suggested that high nuclear SOX2 expression at the invasive front may predict radiosensitivity.
Scandinavian Journal of Immunology, 1993
Jejunal biopsy specimens from 10 patients with treated coeliac disease and seven non-coeliac cont... more Jejunal biopsy specimens from 10 patients with treated coeliac disease and seven non-coeliac controls were challenged in vitro with peptic-tryptic gluten digest. Mucosal T cells were examined in situ by three-colour immunofluorescence staining for expression of the activation marker CD25 (the p55 alpha-chain of interleukin-2 receptor) and the nuclear proliferation marker revealed by monoclonal antibody Ki-67. Intraepithelial T cells expressed CD25 rarely whereas the proportion of activated lamina propria T cells increased (P &amp;lt; 0.002) from median 2.8% (cultured with 20% fetal calf serum alone for 24-48 h) to 10.0% after 24 h with gluten (n = 10; range 1.1-17.4%) and to 10.4% after 48 h (n = 7; range 1.4-17.5%). Such gluten-induced increase of CD25+ T cells was not observed in specimens from non-coeliac control subjects. Crypt-cell hyperplasia and T-cell proliferation (Ki-67+) were observed neither in the coeliac nor in the control mucosae after gluten stimulation. Three-colour staining combining a polyclonal antibody reagent to CD3 and a monoclonal antibody to CD25 with a monoclonal antibody to CD45R0, CD4, CD8, the p75 beta-chain of interleukin-2 receptor, integrin alpha E beta 7, or HLA-DR showed that most of the CD25+ T cells (&amp;gt; 90%) were CD4+CD8-, co-expressed CD45R0 and the p75 beta-chain, and often also the integrin alpha E beta 7 but not HLA-DR. In addition to these activated T cells, a dominating population of CD25+CD3-CD4+ subepithelial pan-HLA-class II+ macrophages (CD68+) with variable expression of the p75 beta-chain was often induced by gluten challenge.
Immunology
The specialized M cells in the follicle-associated epithelium (FAE) of Peyer's patches (PP) repre... more The specialized M cells in the follicle-associated epithelium (FAE) of Peyer's patches (PP) represent an intimate interphase between luminal antigens and gut-associated lymphoid tissue (GALT). M cells form pockets that contain clusters of leucocytes probably involved in the first encounter with antigens from the gut lumen. Three-colour immunofluorescence in situ phenotyping of these leucocytes in humans revealed about equal numbers of B (CD19/20+) and T (CD3 +) lymphocytes, the latter mainly CD4+ (median 73%, range 40-90%), but relatively few macrophages (CD68 +). Most B cells (90%) were positive for surface IgM (sIgM) and often co-expressed sIgD (median 34%, range 6-60%). Occasional B cells (median 2%) did not express CD45RA (range 0-15%) and 13% virtually lacked HLA-DR (range 0-40%). Some B and T lymphocytes expressed the nuclear proliferation marker Ki-67 (range 1-10%). The M-cell pockets also contained occasional cells with cytoplasmic IgA or IgM. These sites thus contained a heterogeneous B-cell population with features of both follicular mantle (sIgD+ sIgM+) and marginal zone (sIgD-sIgM +) B lymphocytes. Adjacent T lymphocytes were generally of the memory phenotype (CD45RO+). Our findings suggest that the M-cell-associated B lymphocytes represent local extensions of B-cell follicles towards the gut lumen, developed topically to facilitate antigen presentation and diversification of mucosal immune responses. FAE of rats, mice and rabbits6,10,11 contains more B and T
Advances in Experimental Medicine and Biology
In conclusion, the "M(r) 40kD" antigen is expressed on the apical face of colon... more In conclusion, the "M(r) 40kD" antigen is expressed on the apical face of colonic enterocytes often in spatial relation to immune complexes in active UC, apparently targeting an IgG1-mediated autoimmune attack. Thus, our findings support the notion that an autoimmune response to the "M(r) 40kD" antigen, with local production of specific IgG1, is a possible immunopathological mechanism(s) in UC.
Advances in Experimental Medicine and Biology
In conclusion, it appears that gluten induces a non-proliferative activation of CD4+ lamina propr... more In conclusion, it appears that gluten induces a non-proliferative activation of CD4+ lamina propria T cells, but a proliferative activation in the TCR alpha/beta +CD8+ and TCR gamma/delta + IEL subsets. Although the increased density of TCR alpha/beta +CD8+ and TCR gamma/delta + IEL in the coeliac lesion may be secondary to T cell mediated immune activation in the lamina propria, a direct and primary antigen-driven proliferation of IEL (perhaps CD1-dependent29) cannot be excluded.
Advances in Experimental Medicine and Biology
American Journal Of Pathology
In mice, integrin a4f87 is the main receptor used by lymphocytes that home to the Peyer's patches... more In mice, integrin a4f87 is the main receptor used by lymphocytes that home to the Peyer's patches, although L-selectin contributes to the initial interaction with high endothelial venules. Less is known about the expression and function of these adbesion molecules in humans. The distribution of L-selectin and a4f37 on various B-and T-ceU subsets was examined in human Peyer's patches (n = 8) and appendix (n = 4), coUectively caUed gut-associated lymphoid tissue. Multicolor immunophenotyping was performed on cryosections, and dispersed ceUs were examined by flow cytometry. In cryosections, CD45RA + T ceUs around and within interfoUicular high endothelial venules, as weUl as surface (s)IgD' B lymphocytes in the follicle mantles, often expressed abundant L-selectin but only intermediate levels of ac4137. CD45RO+ T ceUs and sIgD-B ceUs expressed higher levels of ac4187 and were often located near putative efferent lymphatics; only a smaU fraction (<20%) of such memory ceUs expressed L-selectin. By flow cytometry, considerably more T than B lymphocytes co-expressed L-selectin and a4137 (40% versus 25% and 67% versus 39%, respectively). In samples with many L-selectin+ ceUs (>30%), more ofthese lymphocytes co-expressed a4j37 than in samples withfew L-selectin+ ceUs. Because L-selectin and a4137 were co-expressed on lymphocytes located near high endothelial venules, and because such co-expression was relatively common when many L-selectin + ceUs werepresent, both ofthese molecules migbt participate in boming to human gut-associated lymphoid tissue. Such homing is probably most pronounced for T lymphocytes that were found to express L-selectin and ac4137 more often than B lymphocytes. The selective and relatively high expression of a4137 on memory ceUs located near efferent lymphatics indicated a different migratory capacity; after exitfrom gutassociated lymphoid tissue, such stimulated cells might bome mainly to mucosal effector sites. (Am J Pathol 1997, 150:187-199) Gut-associated lymphoid tissue (GALT) comprises Peyer's patches (PPs), appendix, and solitary lymphoid follicles scattered throughout the intestinal mucosa. B and T lymphocytes are primed against intestinal antigens in GALT and are subsequently seeded as memory or effector cells to distant mucosal effector sites, especially the gut lamina propria. Such homing is well established for IgA preursor B cells1 and to some extent also for T cells.2'3 Cytokines or other factors in GALT and mesenteric lymph nodes modulate the expression of surface molecules so that the memory lymphocytes and blasts adhere to endothelial cells of venules in mucosal effector tissues and emigrate there.4 Distinct pairs of such receptors and endothelial ligands (addressins) co-
Scandinavian Journal of Immunology
A revived interest in intraepithelial lymphocytes (IEL) has been elicited by several recent repor... more A revived interest in intraepithelial lymphocytes (IEL) has been elicited by several recent reports suggesting that murine and avian intestinal epithelium contains mainly CD3+CD8+ cells expressing the gamma/delta T-cell receptor (TcR) for antigen; this contrasts with systemically distributed T cells which preferentially employ the TcR alpha/beta. An anatomical dichotomy in the distribution of these two T-cell lineages has hence been proposed. Here we report that this concept does not hold true in man. In situ studies with monoclonal TcR-framework antibodies showed that most (70-90%) human intestinal IEL (which are mainly CD3+CD8+) expressed TcR alpha/beta. Moreover, almost half of the intraepithelial CD3+ cells were positive for the smallest (180 kDa) CD45 molecule (UCHL1); this probably reflected that they are antigen-primed and thus represent traditional CD3+CD8+ alpha/beta+ memory T cells.
Scandinavian Journal of Immunology
Halstensen, TS. Scott, H. & Brandtzaeg. P. Inlraepilhelial T Cells ol" the TcRv/.i'... more Halstensen, TS. Scott, H. & Brandtzaeg. P. Inlraepilhelial T Cells ol" the TcRv/.i' CDS and * Phenotypes are Increased in Coeliac Disease. Stand. J. Immunol. 30, 665-672. 1989 Expression of the / I't T-cell receptor (TcR) for aniigen on CD?' intraepiihelial lymphiwytes (lEL) was studied ...
Journal of Experimental Medicine
Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible indivi... more Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA-DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated ...
Advances in Experimental Medicine and Biology
Gastroenterology
Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (I... more Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (IgG) and M (IgM) antibodies to gluten. Intake of dietary gluten may hence induce local complement activation and mucosal damage. Jejunal tissue sections from adult patients with celiac disease were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and the terminal complement complex (TCC). Subepithelial deposition of TCC was observed in 93% of 28 untreated and in 57% of 23 partly treated study subjects. The immunofluorescence staining intensity was well correlated with the serum level of gluten-specific IgG and IgM (but not IgA), the number of mucosal IgG-producing cells, and the degree of villous atrophy. Similar immune deposits were not observed in 5 successfully treated patients with celiac disease, 5 patients with dermatitis herpetiformis without jejunal villous atrophy, and 90% of 21 control patients with histologically normal jejunal mucosa. ...
Immunology
Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha... more Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha/beta or gamma/delta was studied in situ by three-colour immunofluorescence on jejunal tissue sections from 21 patients with coeliac disease and eight controls. CD45RA-TcR alpha/beta+ IEL expressed CD45RO significantly more often (75%) than the preferentially expanded TcR gamma/delta+ counterpart (59%). Triple staining for CD3, CD4/8 and CD45RA or CD45RB revealed that all CD3 + 4 - 8 - IEL (taken to be TcR gamma/delta+) expressed CD45RB and none were CD45RA. CD45RO positivity was of the same magnitude (66%) on the predominating monoclonal antibody delta TCS1-reactive fraction of TcR gamma/delta+ cells as on the remainder of the TcR gamma/delta+ subset. These results suggest that gluten exposition in patients with coeliac disease leads to accumulation of CD45RA-, putative antigen-primed memory cells of both TcR phenotypes. The less marked CD45RO expression within the preferentially expand...
Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxy... more Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and Ll (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myoeardial arterio-venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of Ll increased during CPB from 344+71
Journal of Virology
The proportion of T-cell receptor gamma/delta+ cells and the CD4/CD8 ratio relative to all CD3+ i... more The proportion of T-cell receptor gamma/delta+ cells and the CD4/CD8 ratio relative to all CD3+ intraepithelial lymphocytes (IEL) were determined by immunofluorescence in duodenal mucosa of late-stage (mostly CDC IVC1/D) subjects (n = 21) infected with human immunodeficiency virus type 1 (HIV-1). The gamma/delta fraction (median, 14.2%; range, 1.7 to 59.8%) was increased (P < 0.03) compared with that in HIV- controls (n = 11; median 2.8%; range, 0.3 to 38%). Also, the number of gamma/delta+ IEL per mucosal unit was increased (P < 0.05) in the HIV+ subjects (median, 11.1/U) compared with the controls (3.2/U). Approximately 100% of the gamma/delta+ IEL were CD8-, and most expressed the Vdelta1vJdelta1-encoded epitope (median, 90.9%). The total number of CD3+ IEL tended to be lower than in the controls (67.4 versus 72.9/U). Both the epithelium and the lamina propria contained mainly CD8+ T cells, the median ratios of CD4+ T cells being 1 and 7.6%, respectively. This result accord...
Gastroenterology, 1989
Abbreviations used in this paper: AX, antigen-presenting cell; BALT, bronchus-associated lymphoid... more Abbreviations used in this paper: AX, antigen-presenting cell; BALT, bronchus-associated lymphoid tissue; C, complement; FAE, follicle-associated epithelium; GALT, gut-associated lymphoid tissue; IBD, inflammatory bowel disease; IEL, intraepithelial lymphocyte: IL-Z, interleukin 2; MHC, major histocompatibility complex; pig, polymeric immunoglobulin; pIgA, polymeric (or dimeric) immunoglobulin A; pIgh4, polymeric immunoglobulin M; PP, Peyer's patch: SC, secretory component; SIgA, secretory immunoglobulin A; SIgM, secretory immunoglobulin M
Gut, 1997
It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposit... more It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposition of various activation products of the complement system may contribute to the pathogenesis of chronic gastritis and was therefore studied by immunohistochemistry. Ethanol fixed antrum or body gastric tissue sections from 24 patients infected with H pylori (determined by bacterial immunohistochemistry) and 22 uninfected patients were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and in the terminal complex (TCC). As a control group, biopsy samples from the gastric stump of 23 Billroth II operated patients were studied. Patchy, bright staining for TCC occurred below the surface epithelium and around the glands in H pylori positive and negative gastritis as well as in stump gastritis but seldom in normal mucosa. Activated C3 was present at the apical face of the surface epithelium, significantly more often in the antrum and body from patients...
Advances in experimental medicine and biology, 1995
Bibliotheca nutritio et dieta, 1991
Progress in histochemistry and cytochemistry, 1992
Journal of Oral Pathology & Medicine, 2014
Expression of the stem cell transcription factor SOX2 is often used to imply stemness and poor pr... more Expression of the stem cell transcription factor SOX2 is often used to imply stemness and poor prognosis in cancer. However, its role in oral squamous cell carcinoma (OSCC) is not fully elucidated. Tumour tissues from 62 patients with primary, node negative and non-metastatic OSCCs were used to evaluate SOX2 expression by immunohistochemistry. The results were correlated to clinicopathology, treatment and disease recurrences. The majority of the OSCCs (88%) expressed SOX2. Patients with higher nuclear SOX2 staining intensity in the invasive front compared to the adjacent normal epithelium, had a remarkable longer disease-free period if they received adjuvant post-operative radiotherapy (P = 0.001). This was in particular evident for highly differentiated OSCCs, as none of the high SOX2-expressing tumours reoccurred in contrast to all low SOX2-expressing OSCCs. High nuclear SOX2 expression in the invasive front was associated with dramatic longer disease-free period than low SOX2-expressing carcinomas after post-operative radiotherapy in small OSCCs. The result suggested that high nuclear SOX2 expression at the invasive front may predict radiosensitivity.
Scandinavian Journal of Immunology, 1993
Jejunal biopsy specimens from 10 patients with treated coeliac disease and seven non-coeliac cont... more Jejunal biopsy specimens from 10 patients with treated coeliac disease and seven non-coeliac controls were challenged in vitro with peptic-tryptic gluten digest. Mucosal T cells were examined in situ by three-colour immunofluorescence staining for expression of the activation marker CD25 (the p55 alpha-chain of interleukin-2 receptor) and the nuclear proliferation marker revealed by monoclonal antibody Ki-67. Intraepithelial T cells expressed CD25 rarely whereas the proportion of activated lamina propria T cells increased (P &amp;lt; 0.002) from median 2.8% (cultured with 20% fetal calf serum alone for 24-48 h) to 10.0% after 24 h with gluten (n = 10; range 1.1-17.4%) and to 10.4% after 48 h (n = 7; range 1.4-17.5%). Such gluten-induced increase of CD25+ T cells was not observed in specimens from non-coeliac control subjects. Crypt-cell hyperplasia and T-cell proliferation (Ki-67+) were observed neither in the coeliac nor in the control mucosae after gluten stimulation. Three-colour staining combining a polyclonal antibody reagent to CD3 and a monoclonal antibody to CD25 with a monoclonal antibody to CD45R0, CD4, CD8, the p75 beta-chain of interleukin-2 receptor, integrin alpha E beta 7, or HLA-DR showed that most of the CD25+ T cells (&amp;gt; 90%) were CD4+CD8-, co-expressed CD45R0 and the p75 beta-chain, and often also the integrin alpha E beta 7 but not HLA-DR. In addition to these activated T cells, a dominating population of CD25+CD3-CD4+ subepithelial pan-HLA-class II+ macrophages (CD68+) with variable expression of the p75 beta-chain was often induced by gluten challenge.