3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

DURATION OF HIV EXPOSURE MODULATES THE BREADTH AND THE MAGNITUDE OF HIV-SPECIFIC MEMORY CD4+ T CELLS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuPp0103

Younes S.-A.¹, Trautmann L.², Diab B.Y.², Dumont A.², Kalfayan L.², Kernaleguen A.-E.², Lainesse M.², Boulassel R.³, Routy J.-P.³, Sékaly R.-P.^2
1 NIH, Bethesda, United States of America, ² Université de Montréal, Montréal, Canada, ³ McGill University, Montréal, Canada

INTRODUCTION: In order to characterise the memory HIV specific immune response, it is important to identify the epitopes involved in the primary immune response and define the persistence of these responses. Previous reports have indicated that early HAART treatment helps maintaining broad HIV epitope-specific CD4+ T cells and strong magnitude of Gag-specific CD4+ T cell response. However, little is known about the breadth and the magnitude of HIV-specific CD4+ T cells. Moreover, it is unclear whether early treatment allows the preservation of broad and vigorous HIV-specific CD4+ T cell responses in terms of epitope panel recognition.

METHODS: The goal of this study was to determine the breadth and the magnitude of HIV-specific CD4+ responses by analyzing the CD4+-specific immune response after HAART suppression. We analysed the HIV recognition by CD4+ CFSE-labeled PBMC T cells in 37 successfully HAART-treated patients after one year of therapy using CFSE-based proliferation assay with pools of overlapping peptides spanning the HIV-1 proteins.

RESULTS: CD4+ T cell proliferative responses directed against Gag and Nef epitopes were extremely broad in patients treated between 30 to 180 days after infection. However, patients treated before seroconversion within the first month of infection had restricted breath and magnitude of HIV-specific CD4+ T cell responses, suggesting that a brief exposure to HIV does not allow the generation of HIV-specific memory CD4+ T cells. Patients exposed to HIV for 3 or 4 years before treatment initiation also demonstrate limited HIV-specific CD4+ T cell responses.

CONCLUSIONS: Our data indicate that a short or prolonged exposure to high levels of HIV leads to diminishing HIV-specific CD4+ T cell responses. A better understanding of HIV-specific CD4+ T cell responses in early HAART treated patients could contribute to the design of a vaccine against HIV to restaure a memory compartment efficient and stable in time.

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050724
Basic | TuPp0103 | Lydie Trautmann
HIV-specific cellular immunity

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