Transcription Factor Network Regulating CD+CD8+ Thymocyte Survival

Abstract

More than 80% of thymocytes are CD4(+)CD8(+) double positive (DP) cells subject to positive/ negative selection. The lifespan of DP thymocytes is critical in shaping the peripheral T-cell repertoire essential for mounting immune responses against foreign, but not self, antigens. During T-cell maturation, if the first round of T-cell receptor (TCR) α chain rearrangement fails to generate a productive T-cell receptor, DP cells start another round of α chain rearrangement until positive selection or cell death intervenes. Thus, the lifespan of DP cells determines how many rounds of α chain rearrangement can be carried out, and influences the likelihood of completing positive selection. The antiapoptotic protein Bcl-x(L) is the ultimate effector regulating DP cell survival, and several transcription factors critical for T-cell development, such as TCF-1, E proteins, c-Myb, and RORγt, regulate DP survival via a Bcl-x(L)-dependent pathway. However, the relationship between these transcription factors in this process is largely unclear. Recent results are revealing an interactive network among these critical factors during regulation of DP thymocyte survival. This review will discuss how these transcription factors potentially work together to control DP thymocyte survival that is critical for successful completion of T-cell development.