Sequential development of intraepithelial γδ and αβ T lymphocytes expressing CD8αβ in neonatal rat intestine: requirement for the thymus

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Abstract
Previous studies in congenitally athymic nude rats have suggested that the thymus is important for the development of intestinal T cells. Here we have examined the effect of the nude mutation on intraepithelial lymphocyte (IEL) development from the perinatal period. By immunohistochemistry it was shown that CD3−CD8αα+ putative IEL precursors colonized the epithelium of both normal and athymic neonatal rats. Mature T cells, however, did not develop in athymic neonates. In normal rats, γδ T cells were present at birth and αβ T cells appeared within 8 days of postnatal life. At this age, the composition and relative number of intraepithelial T cells were similar to that in normal adult rats, with the exception that most neonatal T‐cell receptor‐γδ+ and ‐αβ+ IEL expressed CD8β. By contrast, extrathymic T‐cell maturation in the gut of congenitally athymic rats occurred slowly, as CD3+ IEL did not appear until 4–6 months of age. These intraepithelial T cells displayed variable phenotypes and appeared to be induced by environmental antigens as they were not found in isolator‐kept old nudes. In conclusion, the present results indicate that the major colonization of the gut epithelium with γδ and αβ T cells expressing CD8αβ takes place perinatally and requires the presence of the thymus. The developmental relationship between these neonatal T cells and more immature CD3− CD8αα+/− IEL remains elusive.