Differential Appearance of T Cell Subsets in the Large and Small Intestine of Neonatal Mice (original) (raw)
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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
Pediatric Research, 2005
The main objective of this study was to characterize developmental changes in small intestinal intraepithelial lymphocyte (IEL) subpopulations during the suckling period, thus contributing to the understanding of the development of diffuse gut-associated lymphoid tissue (GALT) and to the identification of early mechanisms that protect the neonate from the first contact with diet and gut microbial antigens. The study was performed by double labeling and flow cytometry in IEL isolated from the proximal and distal small intestine of 1-to 21-d-old Lewis rats. During the suckling period, intraepithelial natural killer (NK) cells changed from a typical systemic phenotype, CD8ϩ, to a specific intestinal phenotype, CD8-. Analysis of CD8ϩ IEL revealed a progressive increase in the relative number of CD8ϩ IEL co-expressing TCR␣, cells associated with acquired immunity, whereas the percentage of CD8ϩ cells expressing the NK receptor, i.e. cells committed to innate immunity, decreased. At weaning, IEL maturity was still not achieved, as revealed by a phenotypic pattern that differed from that of adult rats. Thus, late after weaning, the regulatory CD8ϩCD4ϩ
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...
2020
SummaryThe gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneous T cell population with cytotoxic and regulatory properties. Migrating peripheral CD4+ T cells, including regulatory (Treg) and conventional T cells (Tconv), acquire an IEL (CD4-IEL) program upon arrival at the epithelium. However, the specific role of the T cell receptor (TCR) in this process remains unclear. Single-cell TCR repertoire and transcriptomic analysis of intraepithelial CD4+ T cells revealed different extents of clonal expansion and TCR overlap between cell states; fully differentiated CD4-IELs from Tregs or Tconvs were the least diverse. Conditional deletion of TCR on differentiating CD4+ T cells or of MHCII on intestinal epithelial cells prevented CD4-IEL differentiation. However, TCR ablation on developed CD4-IELs did not affect their accumulation. These results indicate that local recognition of a limited set of antigens is an essential signal for the differentiation and ada...
Journal of Experimental Medicine, 1991
Mouse gut intraepithelial lymphocytes (IEL) consist mainly (90%) of two populations of CD8+ T cells. One bears heterodimeric alpha/beta CD8 chains (Lyt-2+, Lyt-3+), a T cell receptor (TCR) made of alpha/beta chains, and is Thy-1+; it represents the progeny of T blasts elicited in Peyer's patches by antigenic stimulation. The other bears homodimeric alpha/alpha CD8+ chains, contains no beta chain mRNA, and is mostly Thy-1- and TCR-gamma/delta + or -alpha/beta +; it is thymo-independent and does not require antigenic stimulation, as shown by its presence: (a) in nude and scid mice; (b) in irradiated and thymectomized mice repopulated by T-depleted bone marrow cells bearing an identifiable marker; (c) in thymectomized mice treated by injections of monoclonal anti-CD8 antibody, which lead to total depletion of peripheral CD8+ T lymphocytes; and (d) in germ-free mice and in suckling mice. In young nude mice, alpha/alpha CD8 chains, CD3-TCR complexes, and TCR mRNAs (first gamma/delta)...
Journal of Experimental Medicine, 1992
Adult athymic, lethally irradiated, Fl -parent bone marrow-reconstituted (AT x BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment . Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts . As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT x BM-SHAM) were essentially void of T cells, whereas in AT x BM thymus-engrafted (AT x BMTHG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT x BM fetal intestine-engrafted (AT x BM-FIG) mice beginning 3 wk postengraftment . Based on H-2 expression, peripheral T cells in AT x BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-a/R+ T cells with both CD4+8 -and CD4 -8+ subsets . Peripheral T cells in AT x BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3e . Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT x BM-FIG and AT x BMTHG mice, though not in spleen cell cultures from AT x BM-SHAM mice . Histologic studies of engrafted tissues 3-4 wk postengraftment
Characterization of T Cell Differentiation in the Murine Gut
Journal of Experimental Medicine, 2002
Gut intraepithelial CD8 T lymphocytes (T-IEL) are distinct from thymus-derived cells and are thought to derive locally from cryptopatch (CP) precursors. The intermediate stages of differentiation between CP and mature T-IEL were not identified, and the local differentiation process was not characterized. We identified and characterized six phenotypically distinct lineagenegative populations in the CP and the gut epithelium: (a) we determined the kinetics of their generation from bone marrow precursors; (b) we quantified CD3-⑀ , recombination activating gene (Rag)-1, and pre-T ␣ mRNAs expression at single cell level; (c) we characterized TCR- , -␥ , and -␣ locus rearrangements; and (d) we studied the impact of different mutations on the local differentiation. These data allowed us to establish a sequence of T cell precursor differentiation in the gut. We also observed that the gut differentiation varied from that of the thymus by a very low frequency of pre-T ␣ chain mRNA expression, a different kinetics of Rag-1 mRNA expression, and a much higher impact of CD3 ⑀ / ␦ and pre-T ␣ deficiencies. Finally, only 3% of CP cells were clearly involved in T cell differentiation, suggesting that these structures may have additional physiological roles in the gut.