AEGiS-15IAC: Impaired cytokine production of virus-specific CD8+ T cells in HIV-1 infected patients.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Impaired cytokine production of virus-specific CD8+ T cells in HIV-1 infected patients.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1050)

Onlamoon N, Pattanapanyasat K, Ansari AA
Center of Excellence for Flow Cytometry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

BACKGROUND: To confirm the impaired IFN-γ production by HIV specific CD8+ T cells in HIV infected patients and to determine whether the failure is due to the influence of anti-retroviral drugs (ART).

METHODS: The frequency and number of the HLA-A1101 HIV-1 nef peptide specific CD8+ T cells were evaluated both quantitatively/qualitatively in a group of 10 chronically HIV-1 infected patients who had no prior history of ART. The measurements included the enumeration of HIV-1 nef peptide specific CD8+ T cells using tetramer technology, HIV-1 nef specific IFN-γ synthesizing cells by ELISPOT and intracellular cytokine staining assays (ICS) and nef peptide induced IFN-γ synthesizing cells by tetramer+ CD8+ T cells. In addition, the ability to reconstitute the HIV nef peptide specific IFN-γ response with the use of cytokines or antibodies against cytokines was analyzed.

RESULTS: Data obtained confirmed the previous reported findings of a failure of a high frequency (70%) of HIV-1 nef peptide spec ific CD8+ T cells to synthesize IFN-γ, which suggests that this failure is not secondary to low viral antigenemia or the effect of ART on immune function. The ICS assay appeared to be relatively more sensitive than the ELISPOT assay in these studies. While the addition of IL-2, anti-CD40L, and allogeneic cells led to partial reconstitution of the IFN-g response, the addition of IL-4, IL-12 or a cocktail of anti-TNF-ialpha, TGF-[beta and IL-10 specific antibodies failed to rescue the response by the tetramer positive cells.

CONCLUSIONS: These data suggest that while the frequency of HIV-1 specific CD8+ T cells is maintained for a considerable period of time during the chronic phase of HIV-1 infection, such cells are non-functional and such dysfunction is not secondary to viral antigen load or the direct effect of ART on immune function. The ability of select agents to partially restore immune function suggests that such strategies need to be explored for immune reconstitution.

Keywords: AEGIS, HIV-1, Antigens, CD8, Tumor Necrosis Factors, T-Lymphocytes, HIV Infections, HIV, Viral Load, CD8-Positive T-Lymphocytes, Acquired Immunodeficiency Syndrome, HIV Long-Term Survivors, Interferon Type II, HIV Antigens, CD4-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Interleukin-2, HIV Core Protein p24, Cytokines, Humans, immunology

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MoOrA1050