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

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-1 alpha and MIP-1 beta mRNA, resulting in a rapid increase in production of MIP-1 alpha and MIP-1 beta 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-1 beta contained 10 times less Gag DNA than did those which failed to produce MIP-1 beta. These data suggest that CD4(+) T cells which produce MIP-1 alpha and MIP-1 beta bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.