New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed, persistently seronegative Kenyan sex workers

Autor: Joshua Kimani, Job J. Bwayo, James A Onyango, Kelly S. MacDonald, Keith R. Fowke, Francis M. Mwangi, Juliaas Oyugi, John Rutherford, Tim Rostron, Francis A. Plummer, Sarah Rowland-Jones, E.N.M. Njagi, Tao Dong, Rupert Kaul, Peter Kiama
Rok vydání: 2001
Předmět:
Zdroj: Immunology Letters. 79:3-13
ISSN: 0165-2478
DOI: 10.1016/s0165-2478(01)00260-7
Popis: A clearer understanding of HIV-1 specific immune responses in highly-exposed, persistently seronegative (HEPS) subjects is important in developing models of HIV-1 protective immunity. HIV-1 specific cytotoxic T-lymphocytes (CTL) have been described in a cohort of HEPS Kenyan sex workers, and recent work has further elucidated these responses. CTL specific for HIV-1 Env were found in the blood of over half the sex workers meeting criteria for HIV resistance, and in some women recognized unmapped epitopes. The proportion of women with Env -specific CTL increased with the duration of uninfected HIV exposure, suggesting that these responses were acquired over time. CD8+ lymphocyte responses directed against predefined HIV-1 CTL epitopes from various HIV-1 genes were found in the blood and genital tract of >50% resistant sex workers, at a ten-fold lower frequency than in infected subjects. The epitope specificity of CD8+ responses differs between HEPS and HIV infected women, and in HEPS the maintenance of responses appears to be dependent on persistent HIV exposure. Several HIV-1 ‘resistant’ sex workers have become HIV infected over the past 6 years, possibly related to waning of pre-existing HIV-specific CTL, and infection has often been associated with a switch in the epitope specificity of CD8+ responses. These findings suggest that vaccine-induced protective HIV immunity is a realistic goal, but that vaccine strategies of boosting or persistent antigen may be necessary for long-lived protection.
Databáze: OpenAIRE
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