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

A clearer understanding of HIV-1 specific immune responses in highly-expose d, persistently seronegative (HEPS) subjects is important in developing mod els of HIV-1 protective immunity. HIV-1 specific cytotoxic T-lymphocytes (C TL) 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 wer e 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 HI V exposure, suggesting that these responses were acquired over time. CD8 lymphocyte responses directed against predefined HIV-1 CTL epitopes from va rious HIV-1 genes were found in the blood and genital tract of > 50% resist ant sex workers, at a ten-fold lower frequency than in infected subjects. T he epitope specificity of CD8 + responses differs between HEPS and HIV infe cted women, and in HEPS the maintenance of responses appears to be dependen t on persistent HIV exposure. Several HIV-1 'resistant' sex workers have be come 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 s witch 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. (C) 2001 Elsevier Science B.V. All rights reserved.