title: Immune reconstitution and viral stimulation are required to restore HIV-specific CD8 T cell responses following advanced infection.
abstract: The extent to which highly active antiretroviral therapy (HAART) restores human immunodeficiency virus (HIV)-specific immunity in advanced infection is unknown. Therefore, we studied how effective therapy affected HIV-specific CD8(+) T cell responses in 4 individuals who had progressed to advanced infection. CD8(+) T cell responses were assessed by cytotoxicity and interferon-gamma (IFN-gamma) production. Proliferative CD4(+) T cell responses against HIV, Candida and mitogen were measured by (3)H-thymidine incorporation. Substantial immune reconstitution indicated by increased CD4(+) and CD8(+) T cell numbers followed suppression of viral replication. This was associated with emergence of HIV-specific cytotoxic T lymphocytes (CTL), but only concurrent with detectable viral replication. Emergent anti-HIV CTL were similar to those at earlier stages of infection in terms of their specificity, function, and CD28 phenotype. However, they were very short-lived in the absence of detectable HIV replication. Antigen-specific CD4(+) T cell responses remained severely compromised. Thus, effective antiretroviral therapy restores the capacity for HIV-specific CTL responses after advanced infection. However, the transient nature of these responses suggests failure to generate stable long-lived memory cells in the absence of HIV-specific helper T cell responses.
authors.affiliation: Immunology Program, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Gamberg
authors.forename: Lisa
authors.initials: L
authors.lastname: Barrett
authors.forename: Ian
authors.initials: I
authors.lastname: Bowmer
authors.forename: Constance
authors.initials: C
authors.lastname: Howley
authors.forename: Michael
authors.initials: M
authors.lastname: Grant
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018106:CD28 Antigens / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D018106:CD28 Antigens; D016655:HIV Core Protein p24; D012367:RNA, Viral