ROLE OF IL-2 IN RAT FETAL THYMOCYTE DEVELOPMENT

Early during rat thymus ontogeny, an important proportion of thymocyte s expresses IL-2R and contains IL-2 mRNA, To investigate the role of t he IL-2-IL-2R complex in rat T cell maturation, we supplied either rec ombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions, The IL-2 treatm ent initially stimulated the growth of thymocytes and, as a result, in duced T cell differentiation, but the continuous addition of IL-2 to r at FTOC, as well as the anti-CD25 administration, resulted in cell num ber decrease and inhibition of thymocyte maturation, These results ind icate that immature rat thymocytes bear functional high-affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation, Modifications in TCR alpha beta repertoire and increased numbers of NKR-P1(+) cells, largely NK c ells, were also observed in IL-2-treated FTOC, Furthermore, IL-2-respo nsiveness of different thymocyte subsets changed throughout thymic ont ogeny, Immature CD4(-)CD8(-) cells responded to IL-2 in two stages, ea rly in thymus development and around birth, in correlation with the ma turation of two distinct waves of thymic cell progenitors, Mature CD8( +) thymocytes maximally responded to IL-2 around birth, supporting a r ole for IL-2 in the increased proliferation of mature thymocytes obser ved in vivo in the perinatal period, Taken together, these findings su pport a role for IL-2 in rat T cell development.