AEGiS-14IAC: P24 gag-specific t helper responses are not negatively associated with viremia in c-clade infected South African Zulu adults.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

P24 gag-specific t helper responses are not negatively associated with viremia in c-clade infected South African Zulu adults.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10087)

Ramduth D, Govender U, Mngqundaniso N, Chetty P, Coovadia HM, Addo M, Altfeld M, Brander C, Walker B, Goulder P, Kiepiela P
University of Natal, NRMSM, Durban, South Africa

BACKGROUND: Studies of B clade infected Caucasians have indicated the central role of HIV-specific p24 Gag-specific T helper responses in the successful control of viraemia. No data is available to address the role of T helper activity in C clade infection.

METHODS: Overlapping peptides spanning p24 Gag were synthesised that corresponded to the C clade consensus sequence. These pooled peptides were incubated with PBMC from study subjects and intracellular interferon-gamma producing cells analysed by flow cytometry. Responses of > 0.03% of CD4+ T cells above background were regarded as significant, with > 100,000 lymphocytes analysed in each subject.

BACKGROUND: IFN-γ production was defined as < 0.03% of CD4+ T cells analysed.

RESULTS: The p24 Gag-specific CD4+ T cell response was evaluated in 152 C clade infected Zulu adults not receiving antiretroviral therapy, living in Durban, South Africa. Significant p24 Gag-specific T helper responses were detectable in 97/142 (68%) of subjects (median: 0.08 % of CD4+ T cells, range 0.03% - 2.05%). There was no significant association between % CD4+ T cells, HIV-specific T helper cell activity, absolute CD4 T cell numbers or CD4 percentage of lymphocytes in the peripheral blood responding to pooled p24 Gag peptides and control of vireamia. There was also no association between the level of the CD4+ T cell response and the level of CD8+ T cell activity in response to the pooled p24 Gag peptides.

CONCLUSION: No negative association exists between IFN-γ production following stimulation with p24 Gag overlapping peptides and control of HIV infection in C clade infected adult Zulu. Other aspects of HIV-specific CD4+ T cell function need to be evaluated, such as proliferative activity, responses towards peptides based on autologous virus sequences and to viral proteins other than p24 Gag in order to understand the role of helper responses in control of C clade virus in this population.

Keywords: AEGIS, Viremia, HIV Infections, Antigens, CD4, T-Lymphocytes, Helper-Inducer, African Continental Ancestry Group, Interferon Type II, South Africa, Adult, pathogenicity, immunology

020707
A10087