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Journal of Virology, November 2008, p. 11181-11196, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01433-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Meritxell Genescà,1,2 Pamela J. Skinner,3 Jung Joo Hong,3 Jun Li,2 Ding Lu,2 Michael B. McChesney,2 and Christopher J. Miller1,2,4,5*

Center for Comparative Medicine,1 California National Primate Research Center, University of California, Davis, Davis, California 95616,2 Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108,3 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine,4 Division of Infectious Diseases, School of Medicine, University of California, Davis, Davis, California 956165

Received 9 July 2008/ Accepted 26 August 2008

The presence, at the time of challenge, of antiviral effector T cells in the vaginal mucosa of female rhesus macaques immunized with live-attenuated simian-human immunodeficiency virus 89.6 (SHIV89.6) is associated with consistent and reproducible protection from pathogenic simian immunodeficiency virus (SIV) vaginal challenge (18). Here, we definitively demonstrate the protective role of the SIV-specific CD8+ T-cell response in SHIV-immunized monkeys by CD8+ lymphocyte depletion, an intervention that abrogated SHIV-mediated control of challenge virus replication and largely eliminated the SIV-specific T-cell responses in blood, lymph nodes, and genital mucosa. While in the T-cell-intact SHIV-immunized animals, polyfunctional and degranulating SIV-specific CD8+ T cells were present in the genital tract and lymphoid tissues from the day of challenge until day 14 postchallenge, strikingly, expansion of SIV-specific CD8+ T cells in the immunized monkeys was minimal and limited to the vagina. Thus, protection from uncontrolled SIV replication in animals immunized with attenuated SHIV89.6 is primarily mediated by CD8+ T cells that do not undergo dramatic systemic expansion after SIV challenge. These findings demonstrate that despite, and perhaps because of, minimal systemic expansion of T cells at the time of challenge, a stable population of effector-cytotoxic CD8+ T cells can provide significant protection from vaginal SIV challenge.

* Corresponding author. Mailing address: CNPRC, UC Davis, One Shields Ave., Davis, CA 95616. Phone: (530) 752-0447. Fax: (530) 752-2880. E-mail: cjmiller{at}ucdavis.edu

{triangledown} Published ahead of print on 10 September 2008.

Journal of Virology, November 2008, p. 11181-11196, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01433-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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