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Cutting Edge: Unusual NK Cell Responses to HIV-1 Peptides Are Associated with Protection against Maternal-Infant Transmission of HIV-1¹

Caroline T. Tiemessen^2,*, Sharon Shalekoff^*, Stephen Meddows-Taylor^*, Diana B. Schramm^*, Maria A. Papathanasopoulos, Glenda E. Gray^¶, Gayle G. Sherman, Ashraf H. Coovadia and Louise Kuhn^||

^* AIDS Virus Research Unit, National Institute for Communicable Diseases, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School; National Health Laboratory Services, Empilweni Clinic, Coronation Women and Children Hospital, Enhancing Childhood HIV Outcomes, University of the Witwatersrand, Johannesburg, South Africa; ^¶ Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa; and ^|| Gertrude H. Sergievsky Center, College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032

Most infants exposed to HIV-1 in utero and at delivery do not acquire infection. We show that mothers and infants who have CD3-negative cells that respond to HIV-1 peptides are substantially less likely to transmit and acquire infection, respectively. The CD3-negative cells, shown to be NK cells, respond with remarkable specificity and high magnitude to HIV-1 peptides from Env (envelope) and Reg (regulatory) protein regions, as measured by a whole blood intracellular cytokine assay only in the context of HIV-1 infection or exposure. These findings identify an important new measure of protective immunity to HIV-1 that highlights the importance of innate immunity in preventing the establishment of HIV-1 infection.

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 study was supported in part by the South African AIDS Vaccine Initiative, the National Institute for Child Health and Human Development (Grant 42402), and the Wellcome Trust. C.T.T. is a Wellcome Trust International Senior Research Fellow (076352/Z/05/Z).

² Address correspondence and reprint requests to Prof. Caroline T. Tiemessen, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, South Africa. E-mail address: carolinet{at}nicd.ac.za

³ Abbreviations used in this paper: ICS, intracellular cytokine staining; Env, envelope (protein); Reg, regulatory (protein).

⁴ The online version of this article contains supplemental material.