Background:  Mucosal exposures to HIV-1 in exposed seronegative men who have sex with men (MSM) may lead to localized immunity, which may serve as one mechanism for relative resistance to HIV-1 infection.  In prior studies, we were unable to consistently demonstrate HIV-specific interferon (IFN) -g-secreting T cells in the peripheral blood of most high risk exposed seronegative MSM.  In this study we examined the possibility that HIV-specific T cells may preferentially localize in the lower genital tract of exposed seronegative MSM. 

Methods:  We measured HIV-specific T cells by IFN-g enzyme-linked immunosorbent (ELISpot) assay in the semen of 18 high-risk exposed seronegative MSM who did not possess the CCR5-Δ32 polymorphism.  We contrasted these results with measurements in 22 MSM with chronic HIV infection. Seminal mononuclear cells (SMC) were isolated from fresh ejaculate by pronase treatment and standard density gradient centrifugation and examined in fresh assays.

Results:  We found that, while HIV-infected men all had HIV-1 Gag-specific responses in their blood, only 59% had Gag-specific responses in seminal T cells. In contrast, while no exposed seronegative men had Gag-specific responses in their blood, 27.8% had seminal Gag-specific T cells. In some cases, detection of mucosal T cell responses appeared to be associated with recent HIV exposure or re-exposure.

Conclusions:  These findings suggest that repeated mucosal HIV-1 exposure can induce localized HIV-specific T cells, and that these cells are unlikely to be detected in peripheral blood. Further longitudinal studies are required to understand whether these responses are durable and correlate with reduced susceptibility to HIV infection in high risk men.