Antigen-specific central memory CD4+ T lymphocytes produce multiple cytokines and proliferate in vivo in humans.

The function of Ag-specific central (T-CM) and effector (T-EM) memory CD4(+) T lymphocytes remains poorly characterized in vivo in humans. Using CD154 as a marker of Ag-specific CD4(+) T cells, we studied the differentiation of memory subsets following anti-hepatitis B immunization. Hepatitis B surface Ag (HBs)-specific memory CD4(+) T cells were heterogeneous and included TCM (CCR7(+)CD27(+)) and T-EM (CCR7(-)CD27(+/-)). HBs-specific T-CM and T-EM shared the capacity to produce multiple cytokines, including IL-2 and IFN-gamma. Several years postimmunization, similar to 10% of HBs-specific memory CD4(+) T cells were in cycle (Ki67(+)) and the proliferating cells were CCR7(+). These results suggest that the model of functional specialization of T-CM and TEM cannot be applied to protein vaccine Ags and support the concept that T-CM are capable of self-renewal and contribute to maintain the pool of memory cells.