Role of BCL6 and PD-1 in CD4 memory T cell development (P1165)

Abstract

Abstract Follicular T helper (TFH) cells have been shown to play an indispensable role within the germinal center (GC). To study the effects of TFH cell loss, our lab has developed a mouse line wherein BCL6, the master transcription factor behind TFH cell differentiation, is conditionally deleted in specific cell subsets (BCL6fl/fl). When mated to Cre-CD4 mice, loss of BCL6 specifically in CD4 T cells resulted in a complete absence of GCs. Data from control mice confirmed the correlation between BCL6 and PD-1 expression, with the highest levels of both found in TFH cells. Further analysis showed the few CD4+ CXCR5+ ICOS+ PD-1hi cells found in BCL6fl/fl Cre-CD4 mice have higher rates of apoptosis than those in control mice. Because previous studies have shown that Bcl6 regulates T cell memory, we investigated whether there were any effects on CD4 T cell memory development and found BCL6fl/fl Cre-CD4 mice have an altered memory cell phenotype, with higher levels of central memory cells and lower effector memory cells than control mice. Furthermore, memory cells in these mice show significantly lower rates of apoptosis as well as surface expression of PD-1. Taken together, this data suggests a complex regulatory network involving BCL6 and PD-1 expression, which effects not only TFH cell differentiation, but the development of CD4 T cells into effector versus central memory cells as well.