AEGiS-15IAC: HIV directly impairs cytotoxic T cell function.

15th International AIDS Conference


Bangkok, Thailand - July 11-16, 2004

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HIV directly impairs cytotoxic T cell function.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10125)

Kitchen SG, Jones NR, LaForge S, Whitmire JK, Vu BA, Galic Z, Brooks DG, Kitchen CM, Zack JA
David Geffen School of Medicine at UCLA, Los Angeles, United States

BACKGROUND: During the course of HIV infection, CD8[+] cytotoxic T lymphocyte (CTL) responses are unable to fully suppress viral replication. It is not clear how this occurs or whether HIV has a direct effect on CTL function. HIV proviral DNA is present in CD8[+] T cells in vivo, however the consequences of HIV infection in this cell type are unknown. Infection of CD8[+] cells occurs via the CD4 molecule, which is induced following costimulation of antigen-naïve CD8+ T cells.

METHODS: We investigated how the CD4 molecule on human CD8[+] T cells contributes to CD8[+] cell functions and the effects of HIV infection on these responses.

RESULTS: In this study we show that ligation of the CD4 molecule expressed on CD8[+] T cells results in increased expression of Interferon-gamma (IFN-γ) and Fas-ligand (FasL), two important CD8[+] T cell effector molecules. Ligation of CD4 also resulted in decreased expression of the IL-15 receptor and CD4 itself. Further, HIV infection down-regulates CD4 cell surface expression and perturbs the IFN-γ, FasL, and cytotoxic responses of CD8 cells. Conclusion We have identified a new role for CD4 in the CD8[+] T cell immune response. This provides a mechanism by which HIV directly impairs CD8[+] T cell function and could help explain the defects in the CTL response in HIV infected individuals.

Keywords: AEGIS, HIV, HIV Seropositivity, T-Lymphocytes, Cytotoxic, Acquired Immunodeficiency Syndrome, HIV Infections, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Antigens, CD8, Antigens, CD4, HIV Core Protein p24, Anti-HIV Agents, Membrane Glycoproteins, FasL protein, Humans, immunology

040711
A10125

Copyright © 2004 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.