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PLoS Pathog. 2009 Oct;5(10):e1000646. doi: 10.1371/journal.ppat.1000646. Epub 2009 Oct 30.

Autocrine production of beta-chemokines protects CMV-Specific CD4 T cells from HIV infection.

Author information

1
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, USA. jcasazza@mail.nih.gov

Abstract

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-1alpha and MIP-1beta mRNA, resulting in a rapid increase in production of MIP-1alpha and MIP-1beta after cognate antigen stimulation. Production of beta-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of beta-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-1beta contained 10 times less Gag DNA than did those which failed to produce MIP-1beta. These data suggest that CD4+ T cells which produce MIP-1alpha and MIP-1beta bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.

PMID:
19876388
PMCID:
PMC2763204
DOI:
10.1371/journal.ppat.1000646
[Indexed for MEDLINE]
Free PMC Article

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