AEGiS-14IAC: Reversible anergy of HIV-specific CD4+ T-cells detected by class II tetramers.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Reversible anergy of HIV-specific CD4+ T-cells detected by class II tetramers.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrA1346)

Diab BY, Breton G, Younes S, Bernard N, MacDonald K, Legault M, Routy JP, Sekaly RP
Universite de Montreal, Montreal, Canada

BACKGROUND: HIV-1 infection is marked by a gradual decline in the number of circulating CD4+ lymphocytes in general and a specific failure to develop functional HIV-1-specific T helper cells in the majority of chronically infected individuals. The major goal of this work was to characterize the presence of HIV-specific CD4+ T cells during primary infection (PI) and to identify their fate during the natural history of HIV infection.

METHODS: To directly assess the HIV-specific CD4+ T cell response in HIV+ individuals, we generated soluble tetrameric HLA-DR molecules from 5 alleles covalently linked to 8 immunogenic and conserved HIV peptides. We then performed a prospective longitudinal study over 3 years on 20 PI patients using HLA-DR tetramer staining and cytokine flow cytometry or CFSE-staining following HIV-specific peptide stimulation in vitro.

RESULTS: Analysis of CFSE-staining on patients treated with HAART shows clearly that proliferative response to several epitopes were present in early treated patients (5 out 7 patients) entered in the study with a low viral load (500<VL<5407 copies/ml) and CD4 cell counts in the normal range (408<CD4<940/ml, m = 600). In most cases (80%), these patients maintain this response overtime. Furthermore, the specific tetramers can stain the CSFE low population. In contrast, patients treated late (n= 11, 15313<VL<3500533 copies/ml and 126<CD4<512, m = 300), no peptide induced proliferative or cytokine response to HIV epitopes was seen although these cells are recognised by specific tetramers in some cases. These patients do recognize recall antigens as detected by the same assays. These anergic cells can be proliferate following SEA or tetramer stimulation.

CONCLUSIONS: Our results show that CD4+ T helper response against multiple HIV antigens is generated during the PI stage but these cells disappear rapidly. Anergic state of CD4 cells may be in part responsible for to the lack of peptide-specific proliferative responses.

Keywords: AEGIS, HIV, Antigens, CD4, HIV Infections, CD4-Positive T-Lymphocytes, HIV-1, Viral Load, Antiretroviral Therapy, Highly Active, HIV Antigens, HIV Seropositivity, T-Lymphocytes, Helper-Inducer, Epitopes, HIV Long-Term Survivors, HLA-DR Antigens, Anti-HIV Agents, Prospective Studies, Oceans and Seas, In Vitro, Human, immunology

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