INDUCTION OF INTERLEUKIN-2 RECEPTOR-BETA CHAIN EXPRESSION BY SELF-RECOGNITION IN THE THYMUS

1-2% of adult mouse thymocytes express the T cell receptor alpha/beta (TCR-alpha/beta) together with the interleukin (IL) 2R beta (p70), but not the alpha (p 55) chain. We show that the previously described alpha/beta-TCR(+)CD4(-)8(-) and the partially overlapping Ly6C(+) thymocytes are contained within this subset. Most IL-2R beta(+) alpha/beta-TCR(+) cells have a mature and activated (heat stable antigen [HSA](-), thymic shared antigen 1 [TSA-1](-), CD44(high), CD69(+)) phenotype. Overrepresentation of V beta 8.2 in both CD4(-)8(-) and CD4 and/or CD8(+) IL-2R beta(+) thymocytes suggests that IL-2R beta expression is induced by a TCR-mediated activation event. In mice transgenic for an H-2K(b)-specific TCR, IL-2R beta(+) cells were abundant under conditions of mainstream negative selection, i.e., in the presence of K-b, but absent under conditions of mainstream positive selection or in a nonselecting environment. Together, these results show that in addition to clonal deletion, self-recognition by immature thymocytes leads to phenotypic maturation of a small subset of thymocytes expressing IL-2R beta. IL-2-deficient mice contain normal numbers of IL-2R beta(+) alpha/beta-TCR(+) thymocytes, indicating that like mainstream T cell development, this minor pathway of positive selection does not depend on IL-2. However, in the absence of IL-2, the CD4/CD8 subset composition of IL-2R beta(+) thymocytes is skewed towards CD4(-)8(+), mostly at the expense of CD4(-)8(-). A possible relevance of this finding for the development of the immune pathology of IL-2-deficient mice is discussed.