Mucosal and systemic immune responses in HIV-1 exposed uninfected individuals

摘要: Human immunodeficiency virus (HIV) is an infectious agent that, for 26 years, has evaded vigorous attempts to invent either a cure or preventive agent. Even though the immunological understanding of HIV’s pathogenesis greatly improved, most knowledge been gained from studies systemic compartments but less mucosal environment, where majority all infections occur. Strangely, some individuals, despite their exposure HIV, seem be susceptible infection, thus categorized as HIV Exposed Uninfected (EU) group. These fortunate escapees can considered nature’s own experiment and, possibly, have lessons teach us about superior ways encounter HIV. That obvious potential application research directed toward formulating vaccine. In present thesis, author evaluated cohort Swedish male homosexual EU subjects with regard immune responses lack thereof, in well compartments. Plasma, cells and samples were collected during period two while each these individuals had continuous sexual relations HIV-positive partners. Questionnaires described behaviors, plasma clinical records available Low-risk HIV-negative recruited controls. The questionnaires revealed that vast exposed through oral ( not anal) route. This low-risk behavior rarely seen exclusive if compared other cohorts. We purified saliva obtain IgA, antibody important mostly at sites. Further, we tested IgA IgA-depleted PBMCbased neutralization assay, evaluate whether any anti-HIV capacity. was indeed salivary which 13 25 could neutralize (in vitro) vs 0 22 neutralizing response sustained almost cases study period. Moreover, HIV-neutralizing capacity also detectable (7 EU, controls) associated partner’s HIV-RNA viral load. suggests natural men acquired, predestined. Also plasma, mediated by IgA; however, antibodies (as saliva) lacked classical HIV-specificity measured ELISA Western Blot. then PBMC group found HIV-specific 3 subjects; this detected both CD4+ CD8+ subsets intracellular staining (ICS). Lastly innate molecules known significantly higher levels CC-chemokines than outcome behavioral aspects subjects, genetic polymorphisms, further strengthen theory environmental causes responses. conclusions work are summarized following four points: 1) low-grade, since it occurred via route, still induce and/or sustain IgA. Therefore, route might applicable vaccine setting. 2) While >50% samples, HIVneutralizing existed lesser extent rarely, T-cells. 3) Amounts soluble increased 4) All against factors, implying such acquired. turn, supposition favors possibility similar stronger induced vaccination.