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 (TR). 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- TR expressed FoxP3, TGFbeta, 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- TR expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4+CD27-CD28- TR significantly decreased after granzyme B or TGFbeta inhibition. The CMV-CD4+CD27-CD28- TR 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- TR. The CMV-CD4+CD27-CD28- TR may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals.
Tovar-Salazar
Adriana
A
University of Colorado Denver School of Medicine, Aurora, CO, USA.
Patterson-Bartlett
Julie
J
Jesser
Renee
R
Weinberg
Adriana
A
D015703:Antigens, CD / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D018106:CD28 Antigens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D053804:Granzymes / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D008213:Lymphocyte Activation; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018106:CD28 Antigens; D015704:CD4 Antigens; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053804:Granzymes