T cell receptor α mutant (TCRα –/–) mice, which spontaneously develop colitis under conventional conditions, did not show any signs of colitis under germ‐free conditions, leaving TCRα –β + cells (β dim cells) and TCRγ δ + cells much reduced. Moreover, TCRα –/– mice with alymphoplastic mutation (aly/aly TCRα –/– mice), which lack Peyer's patches and peripheral lymph nodes, did not suffer from colitis. While both β dim cells and TCRγ δ + cells were present in the colons of aly/aly TCRα –/– mice and aly/+ TCRα –/– mice, cytotoxicity of colonic TCRγ δ + cells in aly/aly TCRα –/– mice was almost abolished. Transfer of TCRγ δ + cells from TCRα –/– mice into scid/scid mice or aly/aly TCRα –/– mice could not induce colitis, but injection of anti‐TCRδ mAb into TCRα –/– mice prevented colitis from developing. Finally, TCRα –/– mice expressing transgenic (Tg) KN6‐TCRγ δ hardly developed colitis, accompanied by colonization of non‐cytotoxic Tg TCRγ δ + cells in their colonic mucosa. These results demonstrate that intestinal resident TCRγ δ + cells may be involved in the exacerbation of inflammatory bowel disease in TCRα –/– mice.
Intraepithelial T lymphocytes in the small intestine (IEL) consist of αβ T‐cell receptor (TCR)‐bearing T cells (αβ‐IEL) and γδ TCR‐bearing T cells (γδ‐IEL). Development and cytolytic activation of αβ‐IEL sharply attenuate in germ‐free (GF) mice fed a natural diet (Nat‐GF), but the number and cytotoxicity of γδ‐IEL are comparable between conventional (CV) and Nat‐GF mice. In this report, we compared the properties of IEL in Nat‐GF mice and GF mice fed antigen‐minimized diet (AgM‐GF mice) of C57BL/6 strain to evaluate an influence of gut antigenic load on IEL development. Numbers of αβ‐IEL and γδ‐IEL in AgM‐GF mice were less by 1.9‐ and 1.4‐fold than those in Nat‐GF mice, respectively. Significant decreases in the proportions of CD4+8−, CD4−8αβ+, and CD4+8+ subsets and a resultant increase in the ratio of CD4−8αα+ subset were evident in αβ‐IEL of Nat‐GF mice compared with CV mice, but the subset constitution of αβ‐IEL was similar between Nat‐GF and AgM‐GF mice. In contrast, relative composition of γδ‐IEL was not different between CV, Nat‐GF, and AgM‐GF mice. αβ‐IEL displayed low cytolytic activity in Nat‐GF mice and were almost deprived of their cytotoxicity under the antigen‐minimized condition. While γδ‐IEL were strongly cytolytic in Nat‐GF mice their cytolytic activity was remarkably reduced in AgM‐GF mice. These results indicate that γδ‐IEL are activated independently of microbial colonization in the gastrointestinal tract but their activation occurs in response to the exogenous antigenic substances other than live micro‐organisms.
We analyzed the cytolytic activity of intraepithelial T cells (IEL) isolated from the small intestines of 2-to 3-month-old mutant mice rendered deficient in different gene (s) In the mouse small intestine, numerous T cells (Ϸ5 ϫ 10 7 ) expressing either T cell receptor (TCR)-␣ (40-70%) or TCR-␥␦ (30-60%) reside above the basement membrane together with the columnar epithelial cells (intestinal intraepithelial T lymphocytes; IEL). IEL are unusual among mouse peripheral T cells in that freshly isolated IEL are capable of killing Fc-receptor-bearing target cells after bridging them with anti-CD3 or anti-TCR mAbs (1-3) and in that most ␥␦-IEL and many ␣-IEL, unlike thymus-derived T cells, express a unique CD8␣␣ homodimer (4-7) instead of a CD8␣ heterodimer and develop extrathymically in the intestinal mucosa (4, 5, 7-13). Nevertheless, the functional role of IEL and the precise extrathymic developmental events involving the segregation of ␣-and ␥␦-IEL lineages are not well understood.Owing We have previously shown that the cytolytic activity of ␥␦-IEL is strain-dependent in conventional mice (3) and that this strain-dependent variability is unaltered in the germ-free condition (21). In contrast, the cytolytic activity of ␣-IEL is the hallmark of in situ activation by intestinal microorganisms, which is absent in germ-free mice (1, 2, 21). In the present study, we found that ␥␦-IEL from 2-to 3-month-old  Ϫ͞Ϫ mice fail to display cytolytic activity, whereas ␥␦-IEL from ␣
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