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

The contribution of T cell precursors from the thymus and the bone marrow to the pool of intestinal intraepithelial lymphocytes (IELs) has been studied in a system using donor cells from enhanced-green fluorescent protein (EGFP(+)) transgenic mice adoptively 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 numbers 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 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. (C) 2000 Elsevier Science B.V. All rights reserved.