THE EFFECT OF IN-VIVO IL-7 DEPRIVATION ON T-CELL MATURATION

A number of previous studies have suggested a key role for interleukin 7 (IL-7) in the maturation of T lymphocytes. To better assess the fun ction of IL-7 in lymphopoiesis, we have deprived mice of IL-7 in vivo by long-term administration of a neutralizing anti-IL-7 antibody. In a previous report (Grabstein, K. H., T. J. Waldschmidt, ED. Finkelman, B. W. Hess, A. R. Alpert, N. E. Boiani, A. E. Namen, and P. J. Morriss ey. 1993. J. Exp. Med 178:257-264), we used this system to demonstrate the critical role of IL-7 in B cell maturation. After a brief period of anti-IL-7 treatment, most of the pro-B cells and all of the pre-B a nd immature B cells were depleted from the bone marrow. In the present report, we have injected anti-IL-7 antibody for periods of up to 12 w k to determine the effect of in vivo IL-7 deprivation on the thymus. T he results demonstrate a >99% reduction in thymic cellularity after ex tended periods of antibody administration. Examination of thymic CD4- and CD8- defined subsets revealed that, on a proportional basis, the C D4+, CD8+ subset was most depleted, the CD4 and CD8 single positive ce lls remained essentially unchanged, and the CD4-, CD8- compartment act ually increased to similar to 50% of the thymus. Further examination o f the double negative thymocytes demonstrated that IL-7 deprivation di d, indeed, deplete the CD3-, CD4-, CD8- precursors, with expansion of this subset being interupted at the CD44+, CD25+ stage. The proportion al increase in the CD4-, CD8- compartment was found to be due to an ac cumulation of CD3+, T cell receptor alpha,beta+ double negative T cell s. Additional analysis revealed that anti-IL-7 treatment suppressed th e audition/selection process of T cells, as shown by a significant red uction of single positive cells expressing CD69 and heat stable antige n. Finally, the effects of IL-7 deprivation on the thymus were found t o be reversible, with a normal pattern of thymic subsets returning 4 w k after cessation of treatment. The present results thus indicate a ce ntral role for IL-7 in the maturation of thymic-derived T cells.