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Journal of Virology, March 2006, p. 2771-2783, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2771-2783.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Th-1-Type Cytotoxic CD8+ T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys

Zichun Wang,1 Benjamin Metcalf,1 Ruy M. Ribeiro,3 Harold McClure,2 and Amitinder Kaur1*

Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,1 Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322,2 Los Alamos National Laboratory, Los Alamos, New Mexico 875453

Received 25 August 2005/ Accepted 14 December 2005

Sooty mangabeys are a natural host of simian immunodeficiency virus (SIV) that remain asymptomatic and do not exhibit increased immune activation or increased T-lymphocyte turnover despite sustained high levels of SIV viremia. In this study we asked whether an altered immune response to SIV contributes to the lack of immunopathology in sooty mangabeys as opposed to species with pathogenic lentivirus infection. SIV-specific cellular immune responses were investigated in a cohort of 25 sooty mangabeys with natural SIV infection. Gamma interferon (IFN-{gamma}) enzyme-linked immunospot (ELISPOT) assay responses targeting a median of four SIV proteins were detected in all 25 mangabeys and were comparable in magnitude to those of 13 rhesus macaques infected with SIVmac251 for more than 6 months. As with rhesus macaques, Th2 ELISPOT responses to SIV were absent or >10-fold lower than the IFN-{gamma} ELISPOT response to the same SIV protein. The SIV-specific ELISPOT response was predominantly mediated by CD8+ T lymphocytes; the frequency of circulating SIV-specific CD8+ T lymphocytes ranged between 0.11% and 3.26% in 13 mangabeys. Functionally, the SIV-specific CD8+ T lymphocytes were cytotoxic; secreted IFN-{gamma}, tumor necrosis factor alpha, and macrophage inflammatory protein 1ß; and had an activated effector phenotype. Although there was a trend toward higher frequencies of SIV-specific CD8+ T lymphocytes in mangabeys with lower viral loads, a significant inverse correlation between SIV viremia and SIV-specific cellular immunity was not detected. The consistent detection of Th1-type SIV-specific cellular immune responses in naturally infected sooty mangabeys suggests that immune attenuation is neither a feature of nor a requirement for maintenance of nonpathogenic SIV infection in its natural host.

* Corresponding author. Mailing address: Division of Immunology, New England Primate Research Center, Harvard Medical School, One Pine Hill Dr., Southborough, MA 01772. Phone: (508) 624-8169. Fax: (508) 624-8172. E-mail: amitinder_kaur{at}hms.harvard.edu.

Journal of Virology, March 2006, p. 2771-2783, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2771-2783.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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