CD4 on CD8+T Cells Directly Enhances Effector Function and Is a Target for HIV Infection

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-06, Vol.101 (23), p.8727-8732
• Main Authors: Kitchen, Scott G., Jones, Nicole R., LaForge, Stuart, Whitmire, Jason K., Vu, Bien-Aimee, Galic, Zoran, Brooks, David G., Brown, Stephen J., Christina M. R. Kitchen, Zack, Jerome A., Coffin, John M.
• Format: Article
• Language: English
• Subjects: Antigen presenting cells; B lymphocytes; Biological Sciences; CD4 Antigens - metabolism; CD8-Positive T-Lymphocytes - immunology; Cells; Cytotoxicity, Immunologic; Dendritic cells; Fas Ligand Protein; HIV; HIV infections; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immunology; In Vitro Techniques; Infections; Interferon-gamma - metabolism; Ligation; Membrane Glycoproteins - metabolism; Microbiology; Models, Immunological; Molecules; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0401500101

Costimulation of purified CD8+T lymphocytes induces de novo expression of CD4, suggesting a previously unrecognized function for this molecule in the immune response. Here, we report that the CD4 molecule plays a direct role in CD8+T cell function by modulating expression of IFN-γ and Fas ligand, two important CD8+T cell effector molecules. CD4 expression also allows infection of CD8 cells by HIV, which results in down-regulation of the CD4 molecule and impairs the induction of IFN-γ, Fas ligand, and the cytotoxic responses of activated CD8+T cells. Thus, the CD4 molecule plays a direct role in CD8 T cell function, and infection of these cells by HIV provides an additional reservoir for the virus and also may contribute to the immunodeficiency seen in HIV disease.