Autocrine Production of β-Chemokines Protects CMV-Specific CD4+ T Cells from HIV Infection

PLoS Pathogens

Michael R. Betts¹  Daniel C. Douek²  Mario Roederer³  Richard A. Koup⁴  David Ambrozak⁴  Ribka Ayana⁴  Joseph P. Casazza⁴  Jason M. Brenchley⁵  Brenna J. Hill⁵ 

[1] Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America;ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America;Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America;Immunopathogenesis Unit, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, United States of America

关键词: T cells;    HIV infections;    Memory T cells;    Cell staining;    HIV;    Chemokines;    Cytotoxic T cells;    Cytokines;   

DOI  :  10.1371/journal.ppat.1000646

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Induction of a functional subset of HIV-specific CD4+ T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4+ T cells, which are less frequently infected than HIV-specific CD4+ T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4+ T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4+ T cells rapidly up-regulated production of MIP-1α and MIP-1β mRNA, resulting in a rapid increase in production of MIP-1α and MIP-1β after cognate antigen stimulation. Production of β-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of β-chemokines by CD4+ T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4+ T cells. We found that CMV-specific CD4+ T cells which produced MIP-1β contained 10 times less Gag DNA than did those which failed to produce MIP-1β. These data suggest that CD4+ T cells which produce MIP-1α and MIP-1β bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.

【 授权许可】

CC BY