title: Antiretroviral therapy-induced dominant interleukin-2 HIV-1 Gag CD4+ T cell response: evidence of functional recovery of HIV-1-specific CD4+ T cells.
abstract: Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV-1-specific T cells. However, it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral-specific immune response. To study this issue, we analysed the quantitative and qualitative differences of HIV-1-specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals. HIV-1 Gag and staphylococcal enterotoxin B (SEB)-reactive T cells were determined by flowcytometric intracellular secretion of IFN-γ or/and ΙL-2. ART resulted in increase of single IL-2 and decrease of single IFN-γ-secreting HIV-1 CD4+ T cells, while both cytokines secreting HIV-1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL-2 and positively with single IFN-γ-secreting HIV-1 CD4+ cells. Single IL-2 HIV-1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis, a dominant IL-2 HIV-1 CD4+ T cell response (> 70% single IL-2) was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV-1 CD4+ T cell responses were detected even in naive individuals with high viremia. In conclusion, the presence of dominant IL-2 HIV-1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL-2, indicates that the recovery of HIV-1-specific CD4+ T cell functionality under ART is a feasible goal. Furthermore, polyfunctional HIV-1 CD4+ T cell responses seem not to be directly involved in viral replication control.
authors.affiliation: Immunology Department, General Hospital Athens "LAIKO", Athens, Greece. tsalimalma@hotmail.com
authors.forename: K
authors.initials: K
authors.lastname: Tsalimalma
authors.forename: T
authors.initials: T
authors.lastname: Kordossis
authors.forename: E
authors.initials: E
authors.lastname: Choremi-Papadopoulou
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D007376:Interleukin-2; D054301:gag Gene Products, Human Immunodeficiency Virus