Abstract
Most people exposed to HIV become infected and harbor the virus for life. However, there are several documented cases in which individuals remain uninfected even after multiple exposures to the virus over the course of many years. To better understand the basis of resistance to infection, Stranford et al.1 have examined HIV-exposed/uninfected individuals for evidence of protective immunity. Despite documented exposure, HIV could not be detected by ELISA or PCR in the individuals enrolled in this study, and no HIV-specific antibodies were found in the serum, urine or vaginal secretions. Purified CD4+ cells from exposed/uninfected individuals were susceptible to infection by HIV-1 isolates, including isolates from the individual’s primary sexual partners. This indicates that resistance to infection does not result from the inability of the virus to infect the host’s CD4+ cells. Remarkably, if the CD4+ T cells were exposed to infectious HIV in the presence of the host’s CD8+ T cells, viral replication was greatly suppressed. The protective CD8+ T cells failed to kill targets expressing several different HIV antigens (Env, Gag, Pol and Nef), indicating that these cells were noncytolytic. The actual mechanism(s) of noncytolytic CD8+ T-cell-mediated protection against HIV has yet to be elucidated.
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