Role of Bcl-2 in αβ T Cell Development in Mice Deficient in the Common Cytokine Receptor γ-Chain: The Requirement for Bcl-2 Differs Depending on the TCR/MHC Affinity

Abstract Mice lacking the common cytokine receptor γ-chain (γc) exhibit severely compromised T cell development, with diminished Bcl-2 expression in mature (CD4+ or CD8+) thymocytes and peripheral T cells. Enforced expression of Bcl-2 in these mice partially rescued αβ T cell development but not γδ T cell development. Transgenic expression of the OVA-specific DO11.10 (DO10) TCR also could modestly increase thymocyte numbers, and T cells expressing the transgenic TCR (KJ1-26+ T cells) were found in the periphery. Interestingly, the presence of KJ1-26+ T cells was dependent on the MHC background and was seen in the moderate affinity H-2d/d background but not in the higher affinity H-2d/b background in γc-deficient mice. In contrast, KJ1-26+ T cells exist in the periphery in both the H-2d/d and H-2d/b backgrounds in DO10 transgenic γc wild-type mice. These results suggest that the importance of γc-dependent signals for T cell development differs depending on the affinity of TCR for MHC. Moreover, enforced expression of Bcl-2 had a much greater effect on the development of γc-deficient T cells expressing the DO10 TCR in the high affinity H-2d/b background than in the H-2d/d background, suggesting that γc-dependent Bcl-2 expression influences T cell development in a TCR/MHC-dependent manner.