Peter Lydyard - Academia.edu (original) (raw)

Papers by Peter Lydyard

Journal of immunology (Baltimore, Md. : 1950), 1977

ABSTRACT

Immunology, 1975

Intravenous injection of LPS or allogeneic lymphocytes resulted in impaired maturation of B cells... more Intravenous injection of LPS or allogeneic lymphocytes resulted in impaired maturation of B cells within the bursa of chick embryos. A gradual decline in the sensitivity of embryos towards both agents was reflected by a decrease in the number and size of bursal follicles following injection between 10 and 15 days of embryonation. The hypoplasia of these follicles in embryos injected with lymphocytes on the 10th day was a more sensitive measure of graft-versus-host reaction than splenomegaly. The relevance of results with this model to the aetiology of immunodeficiency diseases has been briefly discussed.

International journal of molecular medicine, 1999

The CD5(+) B cell population is prominent in early life and produce low avidity and, thereby, pol... more The CD5(+) B cell population is prominent in early life and produce low avidity and, thereby, polyreactive antibodies. CD5(+) B cells are receptive to cytokines and interleukin-10 seems to be influential in the regulation of some of these CD5(+) B cells. The question of whether CD5 is a marker of activation or a molecule specific for a B cell lineage remains unresolved because evidence in support or against a separate lineage are still a matter for debate. However, we suggest the possibility of different kind of CD5(+) B cells. Indeed, activated CD5(+) B cells do proliferate, following CD5 engagement, while resting CD5(+) B cells do not. Moreover, three ligands for CD5 have, thus far, been identified but their functional effects are yet unknown. CD5(+) B cells probably play a role in setting up the idiotype network, antigen presentation and tolerance induction. B cells of most of the chronic lymphoid leukemias express CD5 molecules and, surprisingly, these cells may be expanded in n...

Immunology letters, 1995

The percentages of circulating gamma delta T cells and the proportions of these expressing Fc gam... more The percentages of circulating gamma delta T cells and the proportions of these expressing Fc gamma RIII (CD16) or HLA-DR in patients with primary Sjögren's syndrome (pSS) and controls were determined using monoclonal antibodies and flow cytometry. There was no significant difference in the percentages of gamma delta T cells in the pSS patients compared with controls. There was, however, a significant increase in the proportions of both CD16+ and HLA-DR+ gamma delta T cells in pSS patients. A 3-colour immunofluorescence technique demonstrated that these two markers were mutually exclusive and therefore may identify either subpopulations of gamma delta T cells or different stages of the activation process.

Pathology, research and practice, 1981

Annales d'immunologie

We conclude that our data are most consistent with the hypothesis that individual bursal stem cel... more We conclude that our data are most consistent with the hypothesis that individual bursal stem cells give rise to multiple clones of B lymphocytes by a preprogrammed sequence of variable (V) region genes. The alternate hypothesis that each stem cell gives rise to one B cell expressing but one set of VH genes could only fit our data if the additional assumption is made that each stem cell is preprogrammed to give rise to an unique B-cell clonotype at a fixed time during development. Since we were unable to influence the pattern of expression of clonotypic diversity by modifying the exposure to antigens and since random somatic mutations would seem an inefficient mechanism for systematic generation of the diversity, we favor the possibility of a genetic mechanism involving an orderly pairing of germ-line VH and VL genes. The corollary of this hypothesis is that V-region diversity is generated first and Ig-class diversity is secondarily expressed within each clone by a switch mechanism ...

Lupus, 1991

Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM λ derived from a 12-week human fetu... more Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM λ derived from a 12-week human fetus. Two binding site idiotypes (BEG-2 Id α and BEG-2 Id β) have been defined with the use of polyclonal rabbit anti-idiotypic anti-serum. BEG-2 Id α is located on the & l a m b d a ; light chain and has been described previously. The BEG-2 Id β is present on the μ heavy chain. By means of a direct binding ELISA, BEG-2 Id β has been identified on EBV-derived mAbs from human fetal liver or spleen (5%), human cord blood (2.7%) and adult peripheral blood (1%). In addition, the Id is present on 8.5% of adult spleen-derived hybridoma antibodies and 6% of RA synovium-derived hybridoma antibodies. In all populations the presence of the Id is associated with binding to DNA and other polyanions. Competition indicated that the Id was located at or near the antigen-binding site on these molecules. To explore the structural basis of this binding, a major part of the BEG-2 chain was sequenced and found to be encoded by a member of the V H 4 family joined to a variant of J H 5 by a very short Diversity or N region. Of the BEG-2 Id β positive mAbs for which the V H family has been determined, five are encoded by V H 4 and two are encoded by V H 6, but none is encoded by other families. Thus, the BEG-2 Id β identifies a set of polyreactive antibodies that are common in fetal life, into adulthood and are encoded by V H 6 and, a subset of V H 4 genes.

This phase I-II study was designed to assess safety and clinical efficacy of SRL172 vaccine in pa... more This phase I-II study was designed to assess safety and clinical efficacy of SRL172 vaccine in patients with advanced stage IV (AJCC) malignant melanoma. Induction of intracellular cytokines (IL-2 and INF-y) in peripheral blood lymphocytes (PBLCs) from these patients was assayed and correlated to clinical outcome. Patients and methods: SRL172 was administered intradermally to 24 patients with stage IV malignant melanoma, initially at 15-day intervals for three vaccinations and then at monthly intervals. Lymphocyte activation for cytokines in PBLCs was assayed prior to each vaccine administration using a FACS-based intracellular cytokine assay. Survival was compared to historical controls. Results: The vaccination schedule resulted in sustained intracellular IL-2 induction in PBLCs in 9 of 23 patients (39%) who received at least three doses. Cytokine induction became apparent within the first three administrations of vaccine and was maximal at 8-12 weeks. Induction of intracellular IL-2 production (group 1) was associated with improved survival (P < 0.036). The median survival of the nine patients demonstrating IL-2 induction was 59 (95% confidence interval (95% CI): 47-71) weeks compared to 31 (95% CI: 18-44) weeks for the non-inducers. Induction of INF-y (group 2) was found in 10 patients and 6 patients had IL-2 and INF-y induction (group 3). There was no survival advantage for these patient groups. Although no objective responses were documented the group as a whole had a median survival of 44 (95% CI: 31-59) weeks which is better than that of historical controls. SRL 172 was safe and well tolerated. Conclusion: SRL 172 is effective in inducing intracellular IL-2 responses in PBLCs of a significant number of patients with stage IV (AJCC) melanoma. This is correlated with improved survival. The survival analysis is sufficiently encouraging to suggest that further prospective trials are justified. The methodology we present in this study may help in developing surrogate markers that will allow rational immunotherapeutic strategies to be designed for cancer patients.

Leukocyte Membrane Determinants Regulating Immune Reactivity, 1976

Publisher Summary This chapter discusses the experiments showing a fast recovery of antigen-bindi... more Publisher Summary This chapter discusses the experiments showing a fast recovery of antigen-binding receptors on immune B lymphocytes, which have previously been treated with an anti-immunoglobulin serum. In the experiment, the rosette-forming cells (RFC) from chicken peripheral blood lymphocytes (PBL) were investigated six days after immunization with sheep red blood cells. All RFC were B-lymphocytes as judged by sensitivity towards specific anti-B and anti-T cell sera. None of the RFC secreted antibody when tested by the haemolytic plaque assay. The mechanism of receptor regeneration was further analyzed by the exposure of antibody-treated and washed cells to various drugs prior to and during incubation. RFC recovery was suppressed by α-methyl-D-mannoside, sodium azide, or cytochalasin B + vinblastine sulfate. The results of the experiment suggest that the dissociation of the receptor antibody complex may play a substantial role during the ligand-induced redistribution process.

Immunology Today, 1999

mmunoglobulin (Ig) is the definitive marker of all B cells, which can secrete antibodies at high ... more mmunoglobulin (Ig) is the definitive marker of all B cells, which can secrete antibodies at high rates as fully mature plasma cells. However, the complexity being defined in the B-cell compartment has required that models based on the concept of a single B-cell population must be reappraised 1. The finding that the T-cell marker CD5 was expressed by a small proportion of normal B cells 2 led to the concept that B cells comprise at least two main subpopulations (B-1 and B-2) 3. B-1 cells encompass the CD5 ϩ subpopulation, whereas B-2 cells represent the conventional B-cell subpopulation. Nevertheless, there is still much debate over their lineage origins, especially in humans, and a great deal of effort has been put into trying to understand the significance of CD5 ϩ B cells in health and disease states. Subpopulations of B cells Advances in leukocyte phenotyping allowed the B-1 subpopulation to be divided into B-1a and B-1b cells (the Ôsister populationÕ). B-1b cells lack cell surface CD5, but share all the other attributes of B-1a cells, such as the presence of the myelomonocytic marker Mac-1 (CD11b/CD18) and the low expression of the high molecular weight isoform of the common leukocyte antigen (CD45RA). However, these cells possess mRNA for CD5 despite the lack of surface CD5 (Ref. 4) and it can be shown that EpsteinÐ Barr virus-stimulated CD5-/CD45RA lo B cells can express CD5 mRNA at levels comparable with those of their surface CD5 ϩ counterparts 5. Unlike mice and humans, other species do not appear to have CD5defined B-cell subpopulations and virtually all the B cells of the rabbit are CD5 ϩ (Ref. 6). The most significant feature of classic B-1 cells, as defined in mouse and humans, is their production of low-affinity polyreactive Igs (Ref. 7). These antibodies recognize a variety of autoantigens and crossreact with many bacterial antigens, including polysaccharides and lipopolysaccharides. In addition, CD5 ϩ B cells show an increased propensity for malignant transformation 8 , and we showed that B cells from patients with chronic lymphocytic leukaemia (CLL) are programmed to produce multispecific autoantibodies 9. Thus, classic B-1 cells appear to be mainly T-cell independent, although they are positively influenced by T-cell-derived cytokines.

Immunology Today, 1987

for rncuse erythro~.ytes (MER +) are present in small numbers in the blood and lymphoid organs of... more for rncuse erythro~.ytes (MER +) are present in small numbers in the blood and lymphoid organs of normal individuals ~,2. More recently, B cells expressing the T cell antigen-CD5, previously termed T1, have also been found in normal blood and lymphoid organs ~. This 67kDa molecule is equivalent to Ly i in the mouse ~ where it has been established that the B cells carrying this marker form a distinct lineage ~. The identification of normal human B cells expressing bo~h CD5 and MER 3 suggests that these are overlapping if not identical cell populations. This is further supported by the fact that chronic lymphocytic leukaemic cells (CLL) of the B-cell type have been shown to be both CD5 and MER + (Ref. 1, 2, 6, 7 and 8). What then is the nature of this B cell population in normal individuals? It is found early in ontogeny 9,~° and large numbers of its cells appear in the circulation following bone marrow transplantation ~. The homolo- gous mur ne B-cell population (Ly 1 +) is also. found early ~n development but in adult life the peritoneal cavity, rather than the bone-marrow is a major source of this population s, MER+/CD5 + B cells, like their murine coun- terparts, express mainly surface IgM and surface IgD (Ref. 2 and 10-12) and either ~ or X light chains (Ref. 11, 13 and Youinou

Transplantation, 1975

Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens re... more Injection of parental bone marrow cells into 12-day-old lethally irradiated F1 hybrid chickens resulted in chimaerism of donor-type graft-versus-host (GVH)-reactive cells and suppression of antisheep red blood cell antibody response. These manifestations of a chronic graft-versus-host reaction were prevented by pretreatment of the donor marrow with specific anti-T cell globulin. In some chimaeras donor-type GVH-reactive cells developed gradually from T cells precursors of donor origin. Transplantation of spleen and marrow cells from sheep red blood cell-primed F1 hybrid donors into lethally irradiated parental recipients resulted in the loss of memory potential within 1-2 weeks of transfer, whereas donor-type IgG allotype synthesis was preserved. Injection of goat antichicken thymocyte serum to recipients 1 day before reconstitution enabled the antibody response of memory cells at 1-2 weeks, although it failed to prevent their rejection by 8-9 weeeks after transplantation. Split chimaerism of donor-type GVH-reactive cells was demonstrated in chickens which had previously rejected the B cells derived from the same graft.

Scandinavian Journal of Rheumatology, 1988

CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on... more CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on a minute fraction of circulating B cells. The number of CD5-expressing B cells is increased in patients with rheumatoid arthritis or primary Sjögren's syndrome. These cells are similar to those leading to chronic lymphocytic leukemia (they may be induced to produce multispecific autoantibodies). Multispecific autoantibodies have also been described in the early B cell repertoire.

Scandinavian Journal of Immunology, 1989

We have previously demonstrated raised levels of IgG and IgA antibody to the mycobacterial 65‐kDa... more We have previously demonstrated raised levels of IgG and IgA antibody to the mycobacterial 65‐kDa heat shock protein (hsp) in the sera of patients with rheumatoid arthritis (RA). We have now attempted to determine whether this phenomenon is specific for RA, and whether it is seen only with the mycobacterial homologue of this particular hsp gene family. We therefore screened antibody levels to the mycobacterial and Escherichia coli hsp 65, and the mycobacterial, E. coli, and human hsp 70, in sera from RA, systemic lupus erythematosus (SLE), tuberculosis (TB), ankylosing spondylitis (AS), Crohn's disease, and control donors. RA sera show the greatest increase in IgA binding to the mycobacterial hsp65, but no increase in IgA binding to the E. coli homologue. Similarly, only RA and TB sera show increased IgG binding to the mycobacterial hsp65, and we have shown previously that the titre is greater in RA. In contrast, the use of mycobacterial and E. coli hsp70 preparations as control...

Scandinavian Journal of Immunology, 1984

A monoclonal antibody, MID 2, which reacts with an epitope common to all human leucocytes, was us... more A monoclonal antibody, MID 2, which reacts with an epitope common to all human leucocytes, was used to show that the leucocyte common antigen can be resolved into four glycoprotein components with molecular weights of 220 K. 200 K, 180 K and 160 K. The 200, 180 and 160 K peptides were all present to various extents in the T and B lymphoblastoid cell lines examined, but the 220 K component was only detected in the B‐cell lines. The 220 K glycoprotein was also lacking in human thymocytes, but evidence of its expression in peripheral blood T lymphocytes was obtained, suggesting that it might be acquired as the cells differentiated. The four glycoproteins isolated from tonsil cells gave similar patterns on peptide mapping by the Cleveland enzymatic method or by cyanogen bromide cleavage, indicating extensive homology. It is conceivable that they differ from each other by the acquisition of simitar repeating domain sequences of approximately 20 K. Alternatively, they may share a common p...

Scandinavian Journal of Immunology, 1990

A minor population of T cells expresses a heterodimeric antigen receptor composed of y and A chai... more A minor population of T cells expresses a heterodimeric antigen receptor composed of y and A chains (TcR‐1). In blood from adults, two subsets of Tγδ cells can be identified by the monoclonalantibodies (MoAb) BB3 and A13. Little is known about the distribution and markers of these subsets early in life. We have therefore examined both the frequencies of these cells in cord blood and their expression of the cytotoxicity‐associated marker serine esterase (SK). using immunocytochemical techniques.Our data show lower percentages of TcR‐1+ cells in the blood of newborns compared with that in adults. However, the ratio of the Al3+/BB3 cells was significantly higher in cord than in adult blood. Whereas virtually all the adult TcR‐1+ cells in blood were SE‐positive. only a small proportion of the cord blood cells earned ibis enzymes. This was; restricted lo the BB3+ Tγδ ‐cell subset in the cord.Our data suggest different characteristics of the TcR‐1+ cells in blood from newborns compared wi...

Scandinavian Journal of Immunology, 1987

Epithelial expression of class II antigens encoded by the major histocompaatility complex (MHC) h... more Epithelial expression of class II antigens encoded by the major histocompaatility complex (MHC) has been proposed as a means by which autoimmune thyroid disease may be initiated and maintained. We studied a rat thyroid epithelial cell line (FRTL‐5), which constitutively expresses class I (OX18) but not class II (OX6orOX17)determinants to quantify in vitro MHC antigen induction using flow cytometry. Recombinant rat γ interferon (rlFN‐γ) induced dosedependent expression of OX6(l‐A) antigen at >48 h (maximum 80–90% of cells in culture at 100 U/ml). whieh was abrogated by DB‐I, a munoclonal antibody to rat IFN‐γ OXI7 antigen (I‐E) was also induced (86%) and OX18 (class I) markedly increased under these conditions Other thyroid‐active agents including the calcium ionophore A23187. dibutyryl cyclic AMP. thyroid‐stimulating autoantibodies from Graves’ disease patients (LATS), and TSH. caused no I‐A induction. Supernatants from spleen cells stimulaled with plant lectins(concanvialin A or...