Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects

CD4(+) CCR6(+) T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6(+) T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3 alpha (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3 alpha inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are few existing reports on the role of MIP-3 alpha in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3 alpha in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin, Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3 alpha was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3 alpha production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3 alpha-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.

Automated summary

HIV infection leads to the inhibition of CCR6 chemokine MIP-3 alpha, resulting in the loss of immune function and the progression of AIDS.