Origins of intestinal intraepithelial lymphocytes: direct evidence for a thymus-derived gamma delta T cell component

The contribution of T cell precursors from the thymus and the bone marrow to the pool of intestinal intraepithelial lymphocvtes (IELs) has been studied in a system using donor cells from enhanced-green fluorescent protein (EGFP+ ) transgenic mice a doptively transferred into EGFP- recipient mice. Consistent with previous studies, regeneration of gamma delta and alpha beta T cell populations in the intestinal epithelium occurred within 2-3 weeks of bone marrow transfer into irradiatiated EGFP- animals and prior to T cell repopulation of the spleen, of interest, however, although transfer of whole adult EGFP+ thymocytes to non-irradiated EGFP- congenitally-athymic nude mice produced alpha beta T cells in both the spleen and intestine. Gamma delta T cells in significant number were detected only in the intestine of recipient mice. In contrast, transfer of CD3-, CD4-, CD8- immature thymocytes resulted in no detectable T cells in either the intestine or the spleen of nude mice up to twelve weeks post-cell transfer, suggesting that intestinal IELs generated from thymocytes arose from differentiated lineage-committed cells rather than from immature thymocytes. These findings provide direct evidence for both thymus-independent and thymus-dependent sources of intestinal gamma delta T cells, and they suggest that murine IELs consist of diverse groups of T cells with distinct developmental origins.