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Development and cytolytic function of intestinal intraepithelial T lymphocytes in antigen‐minimized 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.