Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status

The beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta suppress infection by macrophage-tropic strains of HIV and s imian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of C CR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Coh ort Study at the Baltimore site was conducted to measure chemokine producti on and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC ). Statistical analyses of the data revealed that the production of HIV-sup pressive beta-chemokines by HIV antigen-stimulated PBMC was significantly h igher in HIV-positive subjects without AIDS compared with subjects with cli nical AIDS. increased chemokine production was also correlated with higher proliferative responses to HIV antigens. Both parameters were significantly lower in the AIDS versus non-AIDS group. Notably, significantly higher rev els of MIP-1 alpha were also observed with unstimulated PBMC from seronegat ive subjects at risk for HIV infection released as compared with seropositi ve and non-Multicenter AIDS Cohort Study seronegative subjects. The associa tion of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfec ted status in subjects at risk for infection suggests a positive role for t hese molecules in controlling the natural course of HIV infection.