Resistance to HIV-1 infection among African sex workers is associated withglobal hyporesponsiveness in interleukin4 production

We previously identified HIV-1 resistant prostitutes who remain persistentl y HIV-1 PCR- and antibody-negative despite continued heavy exposure to HIV- 1 through sex work. We hypothesized that differences in virus-specific cyto kine responses are associated with resistance vs. susceptibility to infecti on. Although polyclonal activation failed to reveal such difference, antige n-mediated activation of peripheral blood mononuclear cells (PBMC) in prima ry culture by using intact HIV (IIIB) demonstrates that resistance is assoc iated with enhanced virus-driven interferon gamma and markedly reduced IL-4 responses relative to those seen in HIV-1 seropositive prostitutes (CDC st age A1, CD4>500/ml). No changes were detectable in HIV-stimulated interleuk in (IL) 10 and IL-13 production, but IL-5 responses were somewhat increased in resistant sex workers. Moreover, the IL-4 response of HIV-1 resistant w oman to a panel of unrelated recall antigens were more than 20-fold reduced relative to HIV-infected prostitutes or those of healthy Kenyan women not involved in sex work. Thus, resistant women differ from seropositive-infect ed women and healthy controls by exhibiting a profound global hyporesponsiv eness in their capacity to generate IL-4 responses.