Lack of Infection in HIV-Exposed Individuals Is Associated with a Strong CD8+Cell Noncytotoxic Anti-HIV Response

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 3; pp. 1030 - 1035
• Main Authors: Stranford, Sharon A., Skurnick, Joan, Louria, Donald, Osmond, Dennis, Chang, Sheng-Yung, Sninsky, John, Ferrari, Guido, Weinhold, Kent, Lindquist, Craig, Levy, Jay A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 02.02.1999; National Acad Sciences; National Academy of Sciences
• Subjects: Adult; AIDS; Antibodies; Antivirals; Biological Sciences; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cultured cells; Female; Genotype; HIV; HIV 1; HIV infections; HIV Infections - genetics; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immunity (Disease); Immunity, Innate; Immunology; Infections; Male; Middle Aged; Receptors, CCR5 - genetics; Receptors, CCR5 - immunology; Risk Factors; Sexual Behavior; T-Lymphocyte Subsets - immunology; Virus replication; Virus Replication - immunology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.3.1030

Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8+-cell noncytotoxic inhibition of HIV replication in acutely infected CD4+cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8+-cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 Δ 32 mutation in this population, nor did CD4+cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8+-cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.