Treponema pallidumperiplasmic and membrane proteins are recognized by circulating and skin CD4+ T cells

Abstract

ABSTRACTBackgroundHistologic and serologic studies suggest the induction of local and systemicTreponema pallidum(Tp)-specific CD4+ T cell responses toTpinfection. We hypothesized thatTp-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment.MethodsPBMC collected from 67 participants were screened by IFNγ ELISPOT response toTpsonicate.Tp-reactive T cell lines from blood and skin were probed for responses to 88 recombinantTpantigens. Peptide epitopes and HLA class II restriction were defined for selected antigens.ResultsWe detected CD4+ T cell responses toTpsonicate ex vivo. UsingTp-reactive T cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy,Tp-specific T cells persisted for at least 6 months in skin and 10 years in blood.ConclusionsTpinfection elicits an antigen-specific CD4+ T cell response in blood and skin.Tp-specific CD4+ T cells persist as memory in both compartments long after curative therapy. TheTpantigenic targets we identified may be high priority vaccine candidates.