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Journal of Virology, September 2008, p. 8529-8536, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00183-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Impact of Mucosal Inflammation on Cervical Human Immunodeficiency Virus (HIV-1)-Specific CD8 T-Cell Responses in the Female Genital Tract during Chronic HIV Infection{triangledown}

Pamela P. Gumbi,1 Nonhlanhla N. Nkwanyana,1 Alfred Bere,1 Wendy A. Burgers,1 Clive M. Gray,2 Anna-Lise Williamson,1 Margaret Hoffman,3 David Coetzee,4 Lynette Denny,5 and Jo-Ann S. Passmore1*

Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa,1 National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa,2 Women's Health Research Unit, University of Cape Town, 7925 Cape Town, South Africa,3 School of Public Health, University of Cape Town, 7925 Cape Town, South Africa,4 Department of Obstetrics and Gynaecology, Groote Schuur Hospital, Observatory, Cape Town, South Africa5

Received 25 January 2008/ Accepted 23 May 2008

The female genital tract is the major route of heterosexual human immunodeficiency virus (HIV) acquisition and transmission. Here, we investigated whether HIV-specific CD8 T-cell-mediated immune responses could be detected in the genital mucosa of chronically HIV-infected women and whether these were associated with either local mucosal HIV shedding or local immune factors. We found that CD8+ T-cell gamma interferon responses to Gag were detectable at the cervix of HIV-infected women but that the magnitude of genital responses did not correlate with those similarly detected in blood. This indicates that ex vivo HIV responses in one compartment may not be predictive of those in the other. We found that increased genital tumor necrosis factor alpha (TNF-{alpha}) and interleukin-10 (IL-10) levels correlated significantly with levels of Gag-specific CD8+ T cells at the cervix. Women who were detectably shedding virus in the genital tract had significantly increased cervical levels of TNF-{alpha}, IL-1β, IL-6, and IL-8 compared to women who were not detectably shedding virus. We were, however, unable to detect any association between the magnitude of cervical HIV-specific responses and mucosal HIV shedding. Our results support the hypothesis that proinflammatory cytokines in the female genital tract may promote HIV replication and shedding. In addition, we further show that inflammatory cytokines are associated with increased levels of HIV-specific CD8 effector cells at the genital mucosa but that these were not able to control genital HIV shedding.

* Corresponding author. Mailing address: S3.06.4 Wehner and Beit Building, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, 7925 Cape Town, South Africa. Phone: 27-21-4066089. Fax: 27-21-4066681. E-mail:Jo-ann.Passmore{at}uct.ac.za

{triangledown} Published ahead of print on 18 June 2008.

Journal of Virology, September 2008, p. 8529-8536, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00183-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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