Molecular characterization of gut T cell precursors in euthymic and athymic mice

Abstract

The major compartment of effector T cells in the body lines the epithelium of the murine gut. Intraepithelial T lymphocytes (T-IEL) from this location have large intracytoplasmic storage granules containing perforin and granzyme and express y-INF mRNA.Ex vivothey secrete this lymphokine and kill target cells immediately^{1 3}. The number of these T cells is comparable to that of all T cells present in both spleen and lymph-nodes⁴. T-IEL have different origins in normal mice^5-9. About half derive from activated T cells migrating from the peripheral lymphoid organs to the gut and have a memory phenotype (TcR-aß⁺CD5⁺CD28⁺LFA-1⁺CD44⁺CD8aß⁺or CD4⁺thymus-dependent-IEL/TD-IEL). The other half differs from peripheral T cells by phenotype (CD8aa⁺CD5^-LFA-Y B220⁺) and CD3 complex expression (CD3-4 chain is associated with a analogue, the FcERIy chain¹⁰). They comprise a large proportion of TcR-y8⁺cells, and the TcR-aß⁺cells of this lineage are not deleted by self antigens⁴°¹¹’¹². CD8aa T-IELs are thought to develop locally: structures named cryptopatches, disseminated randomly at the base of some gut crypts containing TcR^-Thy1⁺c-kit⁺IL-7R⁺CD25⁺cells^13,14were assimilated to “local” thymus like structures harboring differentiating precursors^14,15Although CD8aa T-IELs are generated in athymic mice, the presence of a thymus increases their number by five-to 10 fold and modifies their composition⁵’⁷’¹⁶. In euthymic mice, TcR-aß and TcR-y6 T cells are equally represented. In athymic mice about 90-95% of TcR⁺T cells are y8⁺. These differences remain after the injection of peripheral T cells(what reconstitutes TD-IEL), and thus are not due to any role of the TD-IEL on the maturation or expansion of CD8aa T-IEL.