Effects of TH1 and TH2 Cytokines on CD8+Cell Response Against Human Immunodeficiency Virus: Implications for Long-Term Survival

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 24; pp. 11135 - 11139
• Main Authors: Barker, Edward, Mackewicz, Carl E., Levy, Jay A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 21.11.1995; National Acad Sciences
• Subjects: AIDS; AIDS/HIV; Antivirals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cultured cells; Cytokines; Cytokines - physiology; Disease Progression; HIV; HIV infections; HIV Infections - immunology; HIV-1 - growth & development; HIV-1 - immunology; Humans; Immunity, Cellular; Infections; Interleukin-10 - physiology; Interleukin-2 - biosynthesis; Interleukin-4 - physiology; Interleukins; T lymphocytes; Th1 Cells - physiology; Th2 Cells - physiology; Time Factors; Virus Replication
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.24.11135

CD8+cells from long-term survivors [LTS; infected with human immunodeficiency virus (HIV) for 10 or more years and having CD4+cell counts of ≥500 cells per μl] have a 3-fold greater ability to suppress HIV replication than do CD8+cells from patients who have progressed to disease (progressors) during the same time period. A change in the pattern of cytokines produced in the host from those that typically favor cell-mediated immunity (T helper 1, TH1 or type 1) to those that down-regulate it (T helper 2, TH2 or type 2) was investigated as a cause of this reduced CD8+cell anti-HIV function. Treatment of CD8+cells from LTS with the TH1 cytokine interleukin (IL)-2 enhanced their anti-HIV activity, whereas exposure of these cells to TH2 cytokines IL-4 or IL-10 reduced their ability to suppress HIV replication and to produce IL-2. IL-2 could prevent and reverse the inhibitory effects of IL-4 and IL-10. Moreover, prolonged exposure of CD8+cells from some progressors to IL-2 improved the ability of these cells to suppress HIV replication. These observations support previous findings suggesting that strong CD8+cell responses play an important role in maintaining an asymptomatic state in HIV infection. The data suggest that the loss of CD8+cell suppression of HIV replication associated with disease progression results from a shift in cytokine production within the infected host from a TH1 to a TH2 pattern. Modulation of these cytokines could provide benefit to HIV-infected individuals by improving their CD8+cell anti-HIV activity.