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. 2002 Jun 3;195(11):1491-7.
doi: 10.1084/jem.20011793.

A unique subset of self-specific intraintestinal T cells maintains gut integrity

Philippe Poussier  1 , Terri Ning, Diponkar Banerjee, Michael Julius
Affiliations

A unique subset of self-specific intraintestinal T cells maintains gut integrity

Philippe Poussier et al. J Exp Med. .

Abstract

Lymphocytes residing in the intestinal epithelium are exclusively T cells and account for one of the largest collection of T cells in the organism. However, their function remains obscure. We and others have shown that the development of intestinal intraepithelial T cells is compromised in mutant mice prone to chronic intestinal inflammation. These results led us to directly assess their role in regulating the development of colitis secondary to transfer of primary splenic TCRalphabeta(+)CD4(+)CD45RB(hi) T cells into severe combined immunodeficiency (SCID) mice. Here we demonstrate that prior reconstitution of SCID recipients with intraintestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells prevents disease, and does so in an interleukin (IL)-10-dependent fashion. In contrast, reconstitution with either TCRgammadelta(+) or TCRalphabeta(+)CD4(-) CD8alpha(+)beta(+) intestinal T cells did not prevent colitis. TCRalphabeta(+)CD4(-)8alpha(+)beta(-) T cells are unique to the intestinal epithelium of both rodents and humans. Previous repertoire analyses of TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells revealed a high proportion of cells expressing high affinity, self-specific TCR within this subset. We demonstrate that monoclonal, self specific TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) cells derived from TCR transgenic mice also prevent the onset of colitis. Thus, intestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells, selected based on their self-reactivity, maintain gut integrity in a IL-10-dependent fashion.

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Figures

Figure 1.
Figure 1.
Differential susceptibility to colitis in SCID.C57Bl/6 recipients of various iIEL subsets and splenic CD4+CD45RBhiTCRαβ+ T cells. Significant (P < 0.01) protection from colitis was afforded by CD4−CD8α+β−TCRαβ+ iIELs. Results taken from two of the 2–8 experiments performed.
Figure 2.
Figure 2.
Differential susceptibility to colitis in SCID.C57Bl/6 recipients of various iIEL subsets and splenic CD4+45RBhiTCRαβ+ T cells. (A and B) Weight variations over time of experimental groups of recipients. Data represent the mean ± SEM. (A) Statistical significance (Student's t test): no reconstitution (⋄) versus reconstitution with CD4−CD8α+β−TCRαβ+ iIELs (○), P < 0.02; no reconstitution (⋄) versus reconstitution with TCRγδ+ iIELs (♦) or CD4−CD8α+β+TCRαβ+ iIELs (▴), not significant. (B) Reconstitution with CD4−CD8α+β−TCRαβ+ iIELs (○) versus IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs (•), P < 0.05. (C) Pathology scores of individual animals from experimental groups of recipients. Statistical significance (Mann-Whitney test): no reconstitution versus reconstitution with CD4−CD8α+β−TCRαβ+ iIELs, P < 0.002; no reconstitution versus reconstitution with TCRγδ+ iIELs or CD4−CD8α+β+TCRαβ+ iIELs, not significant; reconstitution with CD4−CD8α+β−TCRαβ+ iIELs versus IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs, P < 0.0005; no reconstitution versus reconstitution with IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs, P < 0.05.
Figure 2.
Figure 2.
Differential susceptibility to colitis in SCID.C57Bl/6 recipients of various iIEL subsets and splenic CD4+45RBhiTCRαβ+ T cells. (A and B) Weight variations over time of experimental groups of recipients. Data represent the mean ± SEM. (A) Statistical significance (Student's t test): no reconstitution (⋄) versus reconstitution with CD4−CD8α+β−TCRαβ+ iIELs (○), P < 0.02; no reconstitution (⋄) versus reconstitution with TCRγδ+ iIELs (♦) or CD4−CD8α+β+TCRαβ+ iIELs (▴), not significant. (B) Reconstitution with CD4−CD8α+β−TCRαβ+ iIELs (○) versus IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs (•), P < 0.05. (C) Pathology scores of individual animals from experimental groups of recipients. Statistical significance (Mann-Whitney test): no reconstitution versus reconstitution with CD4−CD8α+β−TCRαβ+ iIELs, P < 0.002; no reconstitution versus reconstitution with TCRγδ+ iIELs or CD4−CD8α+β+TCRαβ+ iIELs, not significant; reconstitution with CD4−CD8α+β−TCRαβ+ iIELs versus IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs, P < 0.0005; no reconstitution versus reconstitution with IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs, P < 0.05.
Figure 3.
Figure 3.
Histological analysis of the colonic mucosa from representative SCID.C57Bl/6 recipients of CD4+CD45RBhiTCRαβ+ T cells and different iIEL subsets. (a) Severe colitis in a SCID.C57Bl/6 recipient of CD4+CD45RBhi TCRαβ+ T cells. (b) Lack of colitis in a SCID.C57Bl/6 recipient of CD4−CD8α+ β−TCRαβ+ iIELs and CD4+CD45RBhi TCRαβ+ T cells. (c) Severe colitis in a SCID.C57Bl/6 recipient of IL-10−/− CD4− CD8α+β−TCRαβ+ iIELs and CD4+CD45RBhi TCRαβ+ T cells. Hematoxylin and eosin stain; original magnification: ×100.
Figure 5.
Figure 5.
Self-specific CD4− CD8α+β−TCRαβ+ iIELs protect SCID.C57Bl/6 recipients of splenic CD4+CD45RBhiTCRαβ+ T cells from colitis. Pathology scores of individual male (□) and female (○) SCID.C57Bl/6 recipients of CD4−CD8α+β− iIELs expressing an HY/Db-specific transgenic TCRαβ, and splenic CD4+CD45RBhiTCRαβ+ T cells derived from male donors. Significant (P < 0.05) protection of male recipients was observed.
Figure 4.
Figure 4.
Protection of SCID.C57Bl/6 recipients of splenic CD4+CD45RBhiTCRαβ+ T cells from colitis by CD4−CD8α+β− TCRαβ+ iIELs is IL-10 dependent. Reconstitution with CD4−CD8α+ β−TCRαβ+ iIEL (○) versus IL-10−/− CD4−CD8α+β−TCRαβ+ iIELs (□), P < 0.008; no reconstitution (▪) versus reconstitution with IL-10−/−CD4−CD8α+β−TCRαβ+ iIELs (□), not significant. Results taken from two of the 3–8 experiments performed.
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References

    1. Powrie, F. 1995. T cells in inflammatory bowel disease: protective and pathogenic roles. Immunity. 3:171–174. - PubMed
    1. Mosley, R.L., D. Styre, and J.R. Klein. 1990. Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras. J. Immunol. 145:1369–1375. - PubMed
    1. Rocha, B., P. Vassalli, and D. Guy-Grand. 1994. Thymic and extrathymic origins of gut intraepithelial lymphocyte populations in mice. J. Exp. Med. 180:681–686. - PMC - PubMed
    1. Poussier, P., P. Edouard, C. Lee, M. Binnie, and M. Julius. 1992. Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes. J. Exp. Med. 176:187–199. - PMC - PubMed
    1. Bandeira, A., S. Itohara, M. Bonneville, O. Burlen-Defranoux, T. Mota-Santos, A. Coutinho, and S. Tonegawa. 1991. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T- cell antigen receptor gamma delta. Proc. Natl. Acad. Sci. USA. 88:43–47. - PMC - PubMed

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