CD4 on CD8+T cells directly enhances effector function and is a target for HIV infection
- 8 June 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (23) , 8727-8732
- https://doi.org/10.1073/pnas.0401500101
Abstract
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-gamma 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-gamma, 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.Keywords
This publication has 63 references indexed in Scilit:
- CD8+ T cells that express CD4 on their surface (CD4dimCD8bright T cells) recognize an antigen-specific target, are detected in vivo, and can be productively infected by T-tropic HIVBlood, 2003
- Simian Immunodeficiency Virus Infection of CD4+CD8+T Cells in a Macaque with an Unusually High Peripheral CD4+CD8+T Lymphocyte CountAIDS Research and Human Retroviruses, 2003
- Upregulation of CD4 on CD8+ T cells: CD4dimCD8bright T cells constitute an activated phenotype of CD8+ T cellsImmunology, 2001
- Response Differences between Human CD4+ and CD8+ T-Cells during CD28 Costimulation: Implications for Immune Cell-Based Therapies and Studies Related to the Expansion of Double-Positive T-Cells during AgingClinical Immunology, 2000
- Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase InhibitorJournal of Biological Chemistry, 1996
- Phenotypic Heterogeneity of Persistent Expansions of CD4+CD8+ T CellsClinical Immunology and Immunopathology, 1994
- Induction of CD4 and susceptibility to HIV-1 infection in human CD8+ T lymphocytes by human herpesvirus 6Nature, 1991
- HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structureCell, 1990
- T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAVNature, 1984
- The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirusNature, 1984