AEGiS-9CROI: Innate Immune Defense Mechanisms Involved in the Control of HIV Replication: Inverse Correlation of HIV Viremia with NK Cell Function.

9th Conference on Retroviruses and Opportunistic Infections

Seattle, Washington - February 24 -February 28, 2002

Innate Immune Defense Mechanisms Involved in the Control of HIV Replication: Inverse Correlation of HIV Viremia with NK Cell Function.

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 25
Kottilil S, Chun TW, Moir S, Liu S, McLaughlin M, Maldarelli F, Fauci AS; NIAID, NIH, Bethesda, MD

BACKGROUND: CD8+ T-cell-mediated viral suppression has been described in HIV-infected individuals. However, the role of the innate immune system in the control of HIV replication is unclear. We examined both cell and soluble factor-mediated suppression of endogenous HIV replication in CD4⁺ T cells from infected individuals by autologous NK cells relative to that of CD8+ T cells.

METHODS: CD4⁺, CD8+, and NK cells were isolated from 12 viremic (5 therapy naïve and 7 treated) and 7 aviremic patients receiving HAART. The CD4⁺ cells were stimulated with anti-CD3 antibody in the following conditions: CD4⁺ cells alone, CD4⁺ cells with CD8+ T cells in co-culture, CD4⁺ cells with NK cells in co-culture, CD4⁺ cells with supernatant from CD8+, and NK cells, in the presence or absence of anti-CC-chemokine antibodies. Levels of HIV-1 p24 and CC-chemokines were measured by ELISA. NK cytotoxicity agianst K562 and intracellular interferon-γ staining were also measured.

RESULTS: NK cells suppressed HIV replication in a co-culture system as effectively as CD8+ cells. Suppression of HIV replication by NK cell culture supernatant was mediated by CC-chemokines and restricted to R5 strains. In contrast, suppression of HIV replication by CD8+ T-cell supernatant involved other as yet unidentified soluble factors in addition to CC-chemokines and was effective against X4 HIV strains. NK cytolytic activity correlated with intracellular interferon-γ staining, but not with the ability of NK cells to control HIV replication in a co-culture system. CC-chemokine-mediated suppression was seen consistently in patients who controlled HIV viremia, but not among patients who had high viremia.

CONCLUSIONS: NK cells potently suppress replication of R5 strains from patients who control viremia comparable to that by CD8+ T cells. NK-mediated suppression of R5 strains involves secretion of CC-chemokines. NK cells exhibit only cell-contact-mediated suppression of X4 strains, whereas CD8+ T cells suppress X4 strains by cell-contact and by soluble factors. NK and CD8+ T cells thus may share common receptors. NK-mediated suppression of HIV R5 strains is attenuated in viremic patients suggesting an HIV-induced inhibitory effect on NK cell function.

Keywords: Viremia, HIV Infections, Virus Replication, Killer Cells, Natural, HIV-1, Antiretroviral Therapy, Highly Active, Antigens, CD8, CD8-Positive T-Lymphocytes, Chemokines, CC, CD4-Positive T-Lymphocytes, Antigens, CD4, T-Lymphocytes, HIV Seropositivity, Anti-HIV Agents, Antigens, CD3, Greece, Human, physiology, prevention & control, virology, immunology

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Copyright © 2002 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.