A novel pathway of thymus-directed T lymphocyte maturation
Lefrançois, L.; Olson, S.
Journal of Immunology 153(3): 987-995
1994
ISSN/ISBN: 0022-1767 PMID: 8027568 Document Number: 428205
Recent evidence has indicated that the intestinal epithelium may be a major extrathymic site of T cell production. However, which of the multiple intestinal intraepithelial lymphocyte (IEL) subsets are extrathymic in origin has been controversial. We now report that the thymus is an integral component of IEL maturation and is required for a novel two-stage process of T cell production. Thus, in neonatally thymectomized mice TCR-gamma-delta IELs were depleted and some TCR-alpha-beta IELs were of an immature phenotype. Thymus grafting experiments revealed that all TCR-gamma-delta and TCR-alpha-beta IEL subsets could be thymus-derived, including TCR-alpha-beta cells lacking Thy1 and CD8-beta. In utero anti-TCR-gamma-delta mAb treatments resulted in depletion of gamma-delta IEL without subsequent re-emergence of this subset in adulthood, whereas anti-TCR-alpha-beta mAb treatment only marginally reduced the alpha-beta IEL subset. These findings suggest that TCR-alpha-beta and TCR-gamma-delta IELs arose at distinct developmental stages. Overall, the results indicate that some IEL precursors are thymus-derived but require further thymic influence to mature in the periphery.