The CD8+ cell non-cytotoxic, anti-HIV response is associated with protection in HIV-exposed, uninfected individuals
Several multiply HIV-exposed, uninfected cohorts were studied for evidence of correlates of protective immunity. This uninfected high risk population was comprised of the IV drug-sharing and/or sexual partners of infected individuals. Genotyping of cells from these HIV-exposed individuals revealed that 29% (14/50) were heterozygous and 4% (2/50) homozygous for the previously identified mutant CCR5 allele (delts32). In vitro infection studies showed that the CD4+ cells from all the individuals tested were susceptible to infection with primary virus strains, including those isolated from their infected partners. None of the high risk individuals tested exhibited evidence of HIV-specific cytotoxic T-lymphocyte responses. However, 50 to 100% of the high risk individuals did manifest a strong CD8+ cell, non-cytotoxic anti-HIV response against either highly cytopathic laboratory virus strains or slower-growing laboratory and primary virus isolates, respectively. This type of immune response was absent in unexposed control subjects. These data demonstrate that high risk individuals remain HIV negative despite having target lymphocytes which are sensitive to HIV infection. Prior exposure of these individuals to HIV appears to induce a protective CD8+ cell noncytotoxic antiviral response not seen in unexposed individuals.
Stranford, S; Skurnick, J; Louria, D; Osmond, D; Chang, SY; Sninsky, J; Ferrari, G; Weinhold, K; Lindquist, C; Levy, J
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