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* Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;
AIDS Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa;
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Nelson R. Mandela School of Medicine, Durban, South Africa;
¶ Human Immunology Section,
|| Immunology Laboratory, and
# ImmunoTechnology Section, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892; and
** Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa
Understanding early immunological events during HIV-1 infection that may set the course of disease progression is important for identifying correlates of viral control. This study explores the association of differentiation profiles of HIV-specific and total memory CD8+ T cells with viral set point. A cohort of 47 HIV-1-infected individuals, with differing viral set points at 12 mo, were recruited during acute infection. We identified that the magnitude of IFN-
+ T cell responses at 6 mo postinfection did not associate with viral set point at 12 mo. A subset of 16 individuals was further studied to characterize CD8+ T cells for expression patterns of markers for memory differentiation, survival (CD127), senescence (CD57), and negative regulation (programmed death-1). We show that viral control and the predicted tempo of HIV disease progression in the first year of infection was associated with a synchronous differentiation of HIV-specific and total CD8+ memory subpopulations. At 6–9 mo postinfection, those with low viral set points had a significantly higher proportion of early differentiated HIV-specific and total memory CD8+ cells of a central memory (CD45RO+CD27+CCR7+) and intermediate memory (CD45RO–CD27+CCR7–) phenotype. Those with high viral set points possessed significantly larger frequencies of effector memory (CD45RO+CD27–CCR7–) cells. The proportions of memory subsets significantly correlated with CD38+CD8+ T cells. Thus, it is likely that a high Ag burden resulting in generalized immune activation may drive differentiation of HIV-specific and total memory CD8+ T cells.
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 funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services Grant U19 A151794; the Canada-Africa Prevention Trials Network; and the Bill and Melinda Gates Comprehensive T Cell Vaccine Immune Monitoring Consortium award. W.B. was supported by a Columbia University-Southern Africa Fogarty AIDS International Training Fellowship.
2 W.A.B. and C.R. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Clive M. Gray, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, South Africa. E-mail address: cgray{at}nicd.ac.za
4 Abbreviations used in this paper: PD-1, programmed death 1; TCM, central memory T cell; TEff, effector T cell; TEM, effector memory T cell; TInt, intermediate memory T cell; TNaive, naive T cell; TTM, transitional memory T cell.
5 The online version of this article contains supplemental material.
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