title: Impaired IFN-gamma production by viral immunodominant peptide-specific tetramer+ CD8+ T cells in HIV-1 infected patients is not secondary to HAART.
abstract: Studies on PBMC samples from HIV-1 infected patients have shown that despite substantial number of HIV specific CTLs, these patients gradually progress to AIDS. The present study was conducted to determine whether this paradox was secondary to the influence of protease inhibitors being utilized by these patients. Thus, aliquots of PBMC samples from 10 HIV infected humans with no prior history of anti-retroviral drug therapy (ART) and 6 HIV-infected patients that had been on HAART for > 1 year were analyzed for the frequency of HIV-1 Nef and Gag dominant peptide specific tetramer+ cells, respectively. The tetramer+ PBMCs were analyzed for their ability to synthesize specific peptide induced IFN-gamma utilizing both the ELISPOT and the intracellular cytokine (ICC) assays. Results of the studies showed that there was an overall correlation between the frequency of Nef and Gag peptide tetramer+ cells and the frequency of IFN-gamma synthesizing cells as assayed by either ICC or ELISPOT assay, markedly reduced values of IFN-gamma synthesizing cells per unit tetramer+ cells were noted in both group of patients. These data suggest that the frequency of HIV-specific CD8+ T cells is maintained during the chronic phase of infection, their ability to function is compromised and is not a reflection of ART. While the addition of IL-2, anti-CD40L and allogeneic cells led to partial increase in the ability of the tetramer+ cells to synthesize IFN-gamma, the addition of IL-4, IL-12, anti-CD28 or a cocktail of antiTGF-beta, TNF-alpha and IL-10 failed to augment the IFN-gamma response.
authors.affiliation: Center of Excellence for Flow Cytometry, Division of Instrument for Research, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Nattawat
authors.initials: N
authors.lastname: Onlamoon
authors.forename: Kovit
authors.initials: K
authors.lastname: Pattanapanyasat
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology; D015693:Gene Products, nef / Q000737:chemistry / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry; D007371:Interferon-gamma / Q000096:biosynthesis*; D020836:Protein Structure, Quaternary; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D015693:Gene Products, nef; D015488:HIV Antigens; D016056:Immunodominant Epitopes; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma