Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy.
HIV-1- and cytomegalovirus (CMV)-specific CD4 T-cell-mediated antiviral immunity was evaluated by assessing the frequency of interleukin 2 (IL-2)- and interferon gamma (IFN-gamma)-secreting cells following antigen-specific stimulation in blood and lymph node. HIV-1-infected subjects with progressive disease at early stage of infection with no previous history of antiretroviral therapy (ART), subjects with nonprogressive disease, and HIV-negative subjects were studied. On the basis of the ability to secrete IL-2 and IFN-gamma, 3 functionally distinct populations of CD4 T cells were identified: (1) IL-2-secreting cells; (2) IL-2/IFN-gamma-secreting cells; and (3) IFN-gamma-secreting cells. CMV-specific CD4 T cells were almost equally distributed within the 3 functionally distinct cell populations in the 3 study groups as well as HIV-1-specific CD4 T cells in subjects with nonprogressive disease. However, a skewing toward IFN-gamma-secreting cells (70% of HIV-1-specific CD4 T cells) was observed in subjects with progressive disease, and IL-2- and IL-2/IFN-gamma-secreting cells were almost absent. The frequencies of IL-2- and of IL-2/IFN-gamma-secreting HIV-1-specific CD4 T cells were negatively correlated with the levels of viremia. Interestingly, prolonged ART was able to correct the skewed representation of different populations of HIV-1-specific CD4 T cells but was associated with only a partial recovery of IL-2-secreting cells. These results indicate that the composition of the pool of functionally distinct virus-specific CD4 T cells is important for virus control.
Harari
Alexandre
A
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue Bugnon, 1011 Lausanne, Switzerland.
Petitpierre
Stéphanie
S
Vallelian
Florence
F
Pantaleo
Giuseppe
G
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D019380:Anti-HIV Agents; D007376:Interleukin-2; D007371:Interferon-gamma