Open AccessAutocrine Production of β-Chemokines Protects CMV-Specific CD4+ T Cells from HIV Infection
Author(s) -
Joseph P. Casazza,
Jason M. Brenchley,
Brenna J. Hill,
Ribka Ayana,
David R. Ambrozak,
Mario Roederer,
Daniel C. Douek,
Michael R. Betts,
Richard A. Koup
Publication year - 2009
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1000646
Subject(s) - chemokine , biology , autocrine signalling , immune system , immunology , t cell , antigen , virology , cell culture , genetics
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.