Striking phenotypic and functional differences in lamina propria lymphocytes from the large and small intestine of mice (original) (raw)
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Scandinavian Journal of Immunology, 1997
Helgeland L, Vaage JT, Rolstad B, Halstensen TS, Midtvedt T, Brandtzaeg P. Regional phenotypic specialization of intraepithelial lymphocytes in the rat intestine does not depend on microbial colonization. Scand J Immunol 1997;46:349-357 Recent studies in mice and humans have provided evidence for regional specialization of gut intraepithelial lymphocytes (IEL). Here the authors report striking regional variability in the composition of IEL in rat small and large intestine. Two-colour immunofluorescence in situ analysis showed that the distribution of the CD3 þ and CD3 ¹ IEL subpopulations varied, the proportion of T cells (CD3 þ ) being higher in the ileum than in the jejunum and smallest in the colon. These differences were explained by variable numbers of the T-cell receptor (TCR)a/b þ (both CD8 þ and CD4 þ ) but not the TCRg/d þ subset. Moreover, the various IEL subpopulations showed distinct intraepithelial distribution patterns with CD4 þ and CD8ab þ T cells situated near the lamina propria, while CD3 ¹ IEL were located preferentially towards the adluminal part of the epithelium. Regional phenotypic variation did not depend on intestinal colonization because analogous results were obtained in germ-free rats. Conventionalization nevertheless caused a marked relative increase of small intestinal TCRa/b þ but not TCRg/d þ IEL. This increase was more sustained in the jejunum than ileum and eventually reduced the phenotypic IEL differences between the two sites. By contrast, microbial colonization of the colon induced only a transient increase of intraepithelial TCRa/b þ cells with no permanent phenotypic alterations. Both CD3 þ and CD3 ¹ IEL contained subpopulations that expressed NKR-P1 independent of intestinal colonization. These results demonstrate phenotypic specialization of IEL at different levels of the gut and suggest that the indigenous flora is not essential to this end.
Veterinary Immunology and Immunopathology, 1993
Vega-Lopez, M A, Telemo, E, Bailey, M, Stevens, K and Stokes, C R, 1993 Immune cell distribution in the small intestine of the pig ~mmunohlstologlcal evidence for an organized compartmentahzatlon in thelamma proprm ¢et Immunol lmmunopathol 37 49-60
Differential function of intestinal intraepithelial lymphocyte subsets
The Journal of Immunology
It has been proposed that intestinal intraepithelial lymphocytes (I-IEL) perform immune surveillance of the epithelial layer (1) and regulate mucosal humoral responses to exogenous Ag (2). To better understand the functional potential of this unique population, purified murine I-IEL were analyzed phenotypically and functionally. Initial studies determined that I-IEL could be distinguished based on several phenotypic characteristics including: TCR (TCR-alpha beta vs TCR-gamma delta); Thy-1, CD45R/B220, CD5, and CD8 (CD8 alpha alpha vs CD8 alpha beta) expression. Using anti-TCR mAb, individual I-IEL subsets were activated and examined functionally. Both TCR-alpha beta and TCR-gamma delta I-IEL were found to synthesize an array of lymphokines that included IL-2, IL-3, and IL-6 but not IL-4 or IL-5. Additionally, a number of lymphokines were detected that directly influence epithelial function (IFN-gamma, TNF-alpha, and TGF-beta 1). However, the majority of the I-IEL function was locali...
Developmental Immunology, 1997
During early neonatal life, important changes occur in the gut. The intestine is challenged by both milk and a microbial flora. Later on, at weaning, the diet of mice changes from milk to pelleted food leading to changes in microbial contents. This period seems essential for a complete development of the mucosal immune system. We investigated the development of both intraepithelial (IEL) and lamina propria lymphocytes (LPL), from day 5, and every 5 days, up to day 30 after birth. IEL and LPL were isolated from the small intestine and the phenotype was assessed by FACS analyses, using antibodies for detection of T-cell markers CD3, TCRαβ, TCRγδ, CD4, CD8α, CD8β, CD5, CD18, CD54, and CD49d. Our data show a clear increase in the number of LPL just before weaning, while the number of IEL increased after day 15. A more mature pattern of membrane antigen expression of both IEL and LPL was observed at weaning. The adhesion molecules CD18, CD54, and CD49d, essential for cellular communicati...
Sequential Appearance of T Lymphocyte Subsets in the Developing Mouse Intestine • 23
Pediatric Research, 1998
We examined the appearance of intestinal intraepithelial lymphocytes (IEL) during the first 12 wk of life to gain insight into postnatal factors that contribute to the differences found between IEL in the large and small intestines of adult mice. Intestinal T cells were very infrequent at birth, but increased in number in the large and small intestine during the first 4 wk of life and then stabilized. The small intestinal epithelium at 2 wk of age contained mostly T cell receptor (TCR) ␣ϩ, CD2ϩ T cells, unlike IEL in adult mice, which were composed of nearly equal proportions of CD2Ϫ, TCR ␣ϩ and TCR ␥␦ϩ cells. Between 2 and 3 wk of age, TCR ␥␦ϩ, CD2Ϫ IEL increased greatly in the small intestine, whereas TCR ␣ϩ cells expressing CD2 decreased. By contrast, IEL in the large intestine at 2 and 3 wk of age were mostly TCR ␣ϩ, CD2ϩ T cells similar to large intestinal IEL in adult mice. And finally, the expression of CD69 increased earlier and to higher levels on TCR ␣ϩ and TCR ␥␦ϩ IEL in the small intestine than in the large intestine. Our ABSTRACT 543
Gut, 1981
Intraepithelial lymphocytes (IEL) of the normal human stomach, small intestine, and large intestine have been characterised in tissue sections by a double marker immunofluorescent technique. A panel of reagents was used in combination, including antisera to T lymphocyte antigen (HuTLA), Ta-like (p28, 33) antigens and immunoglobulin subclasses, as well as a mouse monoclonal antibody to a human leucocyte antigen (HLe-l). In stomach and proximal small intestine over 95 % of IEL were T lymphocytes (HLe-1+, HuTLA+). The proportion was slightly lower in the colon and rectum (85-95 %). IEL rarely expressed Ta-like antigens. B lymphocytes were not seen within the
European Journal of Immunology, 1999
In pigs the lymphocytes emigrating from the intestinal wall were collected by cannulating the lymphatics, labeled in vitro using a fluorescent dye and retransfused. The injection of 6.6 ± 4.2 × 10 8 cells resulted in a labeling index between 1.5 % in intestinal lymph, 0.2 % in the spleen and lymph nodes,˚0.1 % in the intestinal lamina propria and 0.003 % in intraepithelial lymphocytes. About 25 % of the injected cells were present in the blood and 1 % was recovered in the lymph. T cells were found in similar proportions in the injected and the recovered cells in the organs (70-80 %). The proportion of IgA + cells among the immigrated cells in the intestinal lamina propria ranged from 5 to 8 %, which in absolute numbers was up to 60 % of the injected IgA + cells. T and IgM + cells did not show a higher accumulation in any organ. These experiments in conventional, unrestrained animals revealed that (1) T cells immigrate into the intestinal lamina propria, (2) preferential migration of IgA + cells from gut lymph to the intestinal lamina propria is obvious under in vivo conditions and (3) the immigrated IgA + cells represent a very small population which is difficult to detect when analyzed in relative numbers.