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* Research Institute for Genetic and Human Therapy,
Laboratori di Biotecnologie e Tecnologie Biomediche,
Malattie Infettive, and
Servizio di Virologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico S. Matteo, Pavia, Italy;
¶ Georgetown University Medical Center, Washington, DC 20007;
|| McGill University Health Center, Montréal, Québec, Canada; and
# Genetic Immunity, Budapest, Hungary
Evidences have recently suggested that the preservation of vaccine-induced memory rather than effector T cells is essential for better outcome and survival following pathogenic SIV challenge in macaques. However, an equivalent demonstration in humans is missing, and the immune correlates of HIV-1 control have been only partially characterized. We focused on the quantification of Ag-specific T cell precursors with high proliferative capacity (PHPC) using a peptide-based cultured IFN-
ELISPOT assay (PHPC assay), which has been shown to identify expandable memory T cells. To determine which responses correlate with viral suppression and positive immunologic outcome, PBMC from 32 chronically untreated HIV-1-infected individuals were evaluated in response to peptide pools, representing the complete HIV-1 Gag, Nef, and Rev proteins, by PHPC and IFN- ELISPOT assay, which instead identifies effector T cells with low proliferative capacity. High magnitude of Gag-specific PHPC, but not ELISPOT, responses significantly correlated with low plasma viremia, due to responses directed toward p17 and p15 subunits. Only Gag p17-specific PHPC response significantly correlated with high CD4 counts. Analysis of 20 additional PBMC samples from an independent cohort of chronically untreated HIV-1-infected individuals confirmed the correlation between Gag p17-specific PHPC response and either plasma viremia (inverse correlation) or CD4 counts (direct correlation). Our results indicate that the PHPC assay is quantitatively and qualitatively different from the ELISPOT assay, supporting that different T cell populations are being evaluated. The PHPC assay might be an attractive option for individual patient management and for the design and testing of therapeutic and prophylactic vaccines.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo (Grant RCR 08038400 2001 to F.L.). The Women’s Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases with supplemental funding from the National Cancer Institute, and the National Institute on Drug Abuse (U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, and U01-AI-42590). Funding was also provided by the National Institute of Child Health and Human Development (UO1-HD-32632) and the National Center for Research Resources (M01-RR-00071, M01-RR-00079, and M01-RR-00083).
2 Address correspondence and reprint requests to Dr. Franco Lori, Research Institute for Genetic and Human Therapy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, P. le Golgi 2, 27100 Pavia, Italy. E-mail address: rightpv{at}tin.it
3 Abbreviations used in this paper: PHPC, precursors with high proliferative capacity; WIHS, Women’s Interagency HIV Study.
This article has been cited by other articles:
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  R. C. Zahn, M. D. Rett, B. Korioth-Schmitz, Y. Sun, A. P. Buzby, S. Goldstein, C. R. Brown, R. A. Byrum, G. J. Freeman, N. L. Letvin, et al. Simian Immunodeficiency Virus (SIV)-Specific CD8+ T-Cell Responses in Vervet African Green Monkeys Chronically Infected with SIVagm J. Virol., December 1, 2008; 82(23): 11577 - 11588. [Abstract] [Full Text] [PDF]
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