Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection

BACKGROUND: The development of human cytomegalovirus (HCMV)-specific T cell immunity after primary infection and its correlation with virus transmission to the fetus were investigated. METHODS: The membrane phenotype (CCR7 and CD45RA expression) of and intracellular cytokine (interferon [IFN]-gamma and interleukin-2) production by HCMV-specific T cells (stimulated with HCMV-infected dendritic cells) were investigated in 21 immunocompetent pregnant women (12 transmitters and 9 nontransmitters) and in 5 nonpregnant subjects during the first year after infection. RESULTS: IFN-gamma-producing CD4+ and CD8+ T cells were readily detected during the first month, and their levels did not significantly change with time. CCR7 expression was negligible during both the early and the late stage of infection. Among CCR7- cells, those reexpressing CD45RA progressively increased until they reached median levels of 33% (range, 7%-51%) and 51% (range, 22%-76%) for HCMV-specific CD4+ and CD8+ T cells, respectively, similar to those observed in subjects with remote infection. CD45RA reexpression correlated with HCMV disappearance from blood. The level of HCMV-specific CD45RA+ T cells during the first months after infection was significantly lower in mothers who were transmitters than in those who were nontransmitters. CONCLUSIONS: After primary infection, circulating HCMV-specific effector T cells revert to the CD45RA+ phenotype, which appears to be associated with control of viremia and vertical transmission. Thus, these cells may represent long-lived true memory lymphocytes in the HCMV-specific pool.