Bc16 acts as an amplifier for the generation and proliferative capacity of central memory CD8+ T cells

Central memory CD8(+) T cells (T-CM) are considered to be more efficient than effector ones (T-EM) for mediating protective immunity. The molecular mechanism involved in the generation of these cells remains elusive. Because Bcl6 plays a role in the generation and maintenance of memory CD8(+) T cells, we further examined this role in the process in relation to T-CM and T-EM subsets. In this study, we show that T-CM and T-EM were functionally identified in CD62L(+) and CD62L(-) memory (CD44(+)Ly6C(+)) CD8(+) T cell subsets, respectively. Although T-CM produced similar amounts of IFN-gamma and IL-2 to T-EM after anti-CD3 stimulation, the cell proliferation capacity after stimulation and tissue distribution profiles of T-CM differed from those of T-EM. Numbers of T-CM were greatly reduced and elevated in spleens of Bcl6-deficient and lck-Bcl6 transgenic mice, respectively, and those of T-EM were constant in nonlymphoid organs of these same mice. The majority of Ag-specific memory CD8(+) T cells in spleens of these mice 10 wk after immunization were T,,,, and the number correlated with, Bcl6 expression in T cells. The proliferation of Ag-specific memory CD8(+) T cells upon secondary stimulation was dramatically up-regulated in lck-Bcl6 transgenic mice, and the adoptive transfer experiments with Ag-specific naive CD8(+) T cells demonstrated that some of the up-regulation was due to the intrinsic effect of Bcl6 in the T cells. Thus, Bcl6 is apparently a crucial factor for the generation and secondary expansion of T-CM.