HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rollman, E. Articles by Kent, S. J. Search for Related Content PubMed PubMed Citation Articles by Rollman, E. Articles by Kent, S. J.

Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8⁺ T Cells: Implications for HIV Vaccine Strategies¹

Erik Rollman^*, Miranda Z. Smith^*, Andrew G. Brooks^*, Damian F. J. Purcell^*, Bartek Zuber, Ian A. Ramshaw and Stephen J. Kent^2,*

^* Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia; Mabtech, Nacka, Sweden; and John Curtin School of Medical Research, Australian National University, Canberra, Australia

Both the magnitude and function of vaccine-induced HIV-specific CD8⁺ CTLs are likely to be important in the outcome of infection. We hypothesized that rapid cytolysis by CTLs may facilitate control of viral challenge. Release kinetics of the cytolytic effector molecules granzyme B and perforin, as well as the expression of the degranulation marker CD107a and IFN- were simultaneously studied in SIV Gag_164–172 KP9-specific CD8⁺ T cells from Mane-A*10⁺ pigtail macaques. Macaques were vaccinated with either prime-boost poxvirus vector vaccines or live-attenuated SIV vaccines. Prime-boost vaccination induced Gag-specific CTLs capable of only slow (after 3 h) production of IFN- and with limited (<5%) degranulation and granzyme B release. Vaccination with live-attenuated SIV resulted in a rapid cytolytic profile of SIV-specific CTLs with rapid (<0.5 h) and robust (>50% of tetramer-positive CD8⁺ T cells) degranulation and granzyme B release. The cytolytic phenotype following live-attenuated SIV vaccinations were similar to that associated with the partial resolution of viremia following SIV_mac251 challenge of prime-boost-vaccinated macaques, albeit with less IFN- expression. High proportions of KP9-specific T cells expressed the costimulatory molecule CD28 when they exhibited a rapid cytolytic phenotype. The delayed cytolytic phenotype exhibited by standard vector-based vaccine-induced CTLs may limit the ability of T cell-based HIV vaccines to rapidly control acute infection following a pathogenic lentiviral exposure.

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 by Grants 299907 and 251654 from the Australian National Health and Medical Research Council, by the Australian Centre for HIV and Hepatitis Virology Research, and by a 2005-2527 Swedish Research Council Fellowship.

² Address correspondence and reprint requests to Prof. Stephen J. Kent, Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. E-mail address: skent{at}unimelb.edu.au

³ Abbreviations used in this paper: LAV, live-attenuated virus; FPV, fowlpoxvirus; VV, vaccinia virus; ICS, intracellular cytokine staining; LTR, long terminal repeat.

This article has been cited by other articles:

				A. W. Chung, E. Rollman, R. J. Center, S. J. Kent, and I. Stratov Rapid Degranulation of NK Cells following Activation by HIV-Specific Antibodies J. Immunol., January 15, 2009; 182(2): 1202 - 1210. [Abstract] [Full Text] [PDF]

				M. Genesca, P. J. Skinner, J. J. Hong, J. Li, D. Lu, M. B. McChesney, and C. J. Miller With Minimal Systemic T-Cell Expansion, CD8+ T Cells Mediate Protection of Rhesus Macaques Immunized with Attenuated Simian-Human Immunodeficiency Virus SHIV89.6 from Vaginal Challenge with Simian Immunodeficiency Virus J. Virol., November 15, 2008; 82(22): 11181 - 11196. [Abstract] [Full Text] [PDF]

				J. B. Sacha, M. R. Reynolds, M. B. Buechler, C. Chung, A. K. Jonas, L. T. Wallace, A. M. Weiler, W. Lee, S. M. Piaskowski, T. Soma, et al. Differential Antigen Presentation Kinetics of CD8+ T-Cell Epitopes Derived from the Same Viral Protein J. Virol., September 15, 2008; 82(18): 9293 - 9298. [Abstract] [Full Text] [PDF]

				M. Z. Smith, T. E. Asher, V. Venturi, M. P. Davenport, D. C. Douek, D. A. Price, and S. J. Kent Limited Maintenance of Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8 T-Cell Receptor Clonotypes after Virus Challenge J. Virol., August 1, 2008; 82(15): 7357 - 7368. [Abstract] [Full Text] [PDF]

				I. Stratov, A. Chung, and S. J. Kent Robust NK Cell-Mediated Human Immunodeficiency Virus (HIV)-Specific Antibody-Dependent Responses in HIV-Infected Subjects J. Virol., June 1, 2008; 82(11): 5450 - 5459. [Abstract] [Full Text] [PDF]