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

THE LYSISPOT ASSAY REVEALS HIV-SPECIFIC T CELLS CAN LYSE TARGETS WITHOUT SECRETING IFN-γ DIRECTLY EX VIVO, AND THE RELATIVE FREQUENCIES OF IFN-γ SECRETING AND CYTOTOXIC CELLS VARY BOTH AMONGST HIV-SPECIFIC AND IN COMPARISON TO CMV, EBV RESPONSES WITHIN INDIVIDUAL PATIENTS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuPp0104

Snyder-Cappione J.E., Divekar A.A., Maupin G.M., Jin X., Demeter L.M., Mosmann T.R.
University of Rochester Medical Center, Rochester, New York, United States of America

INTRODUCTION: CD8+ T cells are believed to contribute to the containment of the virus and the delay of disease progression in HIV-infected subjects. However, the frequencies of HIV-specific CD8+ T cells, as measured by IFN-γ secretion and tetramer binding, often do not correlate with parameters of disease progression during chronic infection.

METHODS: Using the Lysispot and Elispot assays, we measured the frequencies of cytotoxic and IFN-γ secreting T cells responding to overlapping peptides specific for Gag, Nef, Env, and Pol consensus B sequences, as well as CMV and EBV peptide pools, directly ex vivo from HIV-infected subjects.

RESULTS: PBMC from the majority of HIV-infected subjects contained significant frequencies of HIV-specific cells that killed target cells within five hours directly ex vivo. The relative frequencies of IFN-γ secreting and cytotoxic cells varied markedly between different HIV peptide pools within individual patients; and some HIV-specific responses included T cells able to lyse targets without secreting IFN-γ. Also, neither the ratio of CTL:IFN-γ secreting cells nor the total CTL frequencies specific for different HIV proteins were consistently decreased in comparison to responses specific for two other chronic viral infections, Cytomegalovirus and Epstein Barr virus, within individual subjects. In addition, there was a close association between the frequencies of HIV-specific cytotoxic cells and higher viral loads in chronically infected subjects.

CONCLUSIONS: The IFN-γ and cytotoxic effector functions are independently exerted by individual HIV-specific T cells directly ex vivo from chronically infected subjects. Also, comparisons of these two effector functions between HIV-specific T cells and T cells specific for other chronic infections within individual subjects indicate the HIV-specific T cells are not 'pre-terminally differentiated' as previously suggested. Further analysis of the frequencies of directly cytotoxic T cells may be of considerable value in the assessment of disease progression and the efficacy of HIV vaccines.

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Basic | TuPp0104 | Jennifer E. Snyder-Cappione
HIV-specific cellular immunity

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