Regulatory function of cytomegalovirus-specific CD4+CD27-CD28- T cells

CMV infection is characterized by high of frequencies of CD27(-)CD28(-) T cells. Here we demonstrate that CMV-specific CD4(+)CD27(-)CD28(-) cells are regulatory T cells (T-R). CD4(+)CD27(-)CD28(-) cells sorted from CMV-stimulated PBMC of CMV-seropositive donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose-dependent fashion. Compared with the entire CMV-stimulated CD4(+) T-cell population, higher proportions of CD4(+)CD27(-)CD28(-) T-R expressed FoxP3, TGM, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L CMV-CD4(+)CD27(-)CD28(-) T-R expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4(+)CD27(-)CD28(-) T-R significantly decreased after granzyme B or TGF beta inhibition. The CMV-CD4(+)CD27(-)CD28(-) T-R of HIV-infected and uninfected donors had similar phenotypes and anti-proliferative potency, but HIV-infected individuals had higher proportions of CMV-CD4(+)CD27(-)CD28(-) T-R. The CMV-CD4(+)CD27(-)CD28(-) T-R may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals. (C) 2009 Elsevier Inc. All rights reserved.