Regulatory T-cell activity but not conventional HIV-specific T-cell responses are associated with protection from HIV-1 infection

Objective: Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated on HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4+ T cells, thereby diminishing the likelihood of infection. Methods: To test these hypotheses, we conducted a prospective study among high-risk heterosexual men and women, and tested peripheral blood samples from individuals who subsequently acquired HIV-1 during follow-up (cases) and from a subset of those who remained HIV-1 uninfected (controls). Results: We found no difference in HIV-1-specific immune responses between cases and controls, but Treg frequency was higher in controls as compared with cases and was negatively associated with frequency of effector memory CD4+ T cells. Conclusions: Our findings support the hypothesis that low immune activation assists in protection from HIV-1 infection.