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* Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia;
Melbourne Sexual Health Centre, Carlton, Australia;
Infectious Diseases Department, Alfred Hospital, Prahran, Australia; and
Burnet Institute, Prahran, Australia
Ab-dependent cellular cytotoxicity (ADCC) Abs stimulate NK cell effector functions and play a role in protecting from and controlling viral infections. We characterized ADCC Abs in a cross-sectional cohort of 80 HIV-infected subjects not on antiretroviral therapy. We analyzed ADCC response by killing fluorescently labeled target cells, as well as expression of IFN-
and the degranulation marker CD107a from activated NK cells as measured by a novel intracellular cytokine assay. HIV-specific ADCC directed toward Envelope proteins were present in the majority of 80 untreated HIV-infected individuals measured by killing function. Similarly, most subjects had HIV-specific Abs that mediated degranulation or cytokine expression by NK cells. Interestingly, there was a poor correlation between ADCC-mediated killing of fluorescently labeled whole Envelope protein-pulsed cell lines and Ab-mediated expression of IFN- by NK cells. However, in contrast to healthy donor NK cells, autologous patient NK cells more effectively degranulated granzyme B in response to ADCC activation. Activation of NK cells in response to stimulation by HIV-specific Abs occurs at least as rapidly as activation of Gag-specific CTLs. Our studies highlight the complexity of ab-mediated NK cell activation in HIV infection, and suggest new avenues toward studying the utility of ADCC in controlling HIV 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 Supported by Australian National Health and Medical Research Council awards 299907, 359233, and 251654, and Swedish Research Council Fellowship 2005-2527.
2 Address correspondence to Prof. Kent, Department of Microbiology and Immunology, University of Melbourne, 3010 Australia. E-mail address: skent{at}unimelb.edu.au
3 Abbreviations used in this paper: Nab, neutralizing Ab; ADCC, Ab-dependent cellular cytotoxicity; Env, Envelope; ICS, intracellular cytokine staining; KIR, killer Ig-related receptor; RFADCC, rapid fluorescent ADCC; NCR, natural cytotoxicity receptor.
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  N. Goonetilleke, M. K.P. Liu, J. F. Salazar-Gonzalez, G. Ferrari, E. Giorgi, V. V. Ganusov, B. F. Keele, G. H. Learn, E. L. Turnbull, M. G. Salazar, et al. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection J. Exp. Med., June 8, 2009; 206(6): 1253 - 1272. [Abstract] [Full Text] [PDF]
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