15th International AIDS Conference Bangkok, Thailand — July 11-July 16, 2004

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrA04

M Lichterfeld, D Kaufmann, X Yu, S Mui, M Addo, A Wurcel, D Stone, E Rosenberg, B Walker, M Altfeld
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States

BACKGROUND: Virus-specific CD8+ T cells are associated with declining viremia in acute HIV-1 infection, but do not correlate with control of viremia in chronic infection, suggesting a progressive functional defect not measured by interferon-g assays presently used.

METHODS: Antigen-specific interferon-g secretion and proliferation was simultaneously assessed in 18 individuals with primary HIV-1 infection, 10 persons with chronic progressive HIV-1 infection and 6 patients with chronic long-term non-progressive HIV-1 infection, using an interferon-g Elispot and a CFSE-based proliferation assay, respectively.

RESULTS: HIV-1-specific CD8+ T cells proliferated rapidly upon encounter with cognate antigen in acute infection, but lost this capacity with ongoing viral replication. Ex-vivo depletion of CD4+ T cells or addition of interleukine-2 neutralizing antibodies in acute infection resulted in an almost total abrogation of HIV-1-specific CD8+ T cell proliferation, while autologous CD4+ T cells isolated during acute infection or exogenous IL-2 restored the lymphoproliferative capacity of HIV-1-specific CD8+ T cells in chronic infection.

CONCLUSION: These data demonstrate a loss of CD8+ T cell proliferative function that not only correlates with progressive infection but also can be restored in vitro by augmentation of antigen-specific T helper cell function, providing evidence of a direct functional linkage between these two cellular subsets.

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LbOrA04

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