Human germinal center T cells are unique Thcells with high propensity for apoptosis induction

Collaborative interactions between T-h cells and B cells are necessary for the production of antibody responses to most protein antigens and for the generation of memory B cells in germinal centers (GCs). Although it is well established that T-h Cells are pivotal for the GC reaction, the mechanisms that control the homeostasis of T-h cells during the GC response remain largely unknown. Here we show that, unlike other effector T cells, a significant number of CD4(+)CD45RO(+)CD57(+) T cells, which are the major Th cells residing in the GCs, are undergoing apoptosis in vivo. CD4(+)CD45RO(+)CD57(+) GC T cells exhibit similar sensitivities to apoptotic signals and to caspase inhibitors as immature thymocytes. Moreover, CD4(+)CD45RO(+)CD57(+) GC T cells express a unique profile of genes that control apoptosis and cell cycle, providing possible molecular mechanisms for the high rates of apoptotic death of these T-h cells in the GCs.