Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells.

BACKGROUND: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. METHODS: Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. RESULTS: We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. CONCLUSIONS: T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates.

Treponema pallidum periplasmic and membrane proteins are recognized by circulating and skin CD4+ T cells.

Background: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum ( Tp )-specific CD4+ T cell responses to Tp infection. We hypothesized that Tp -specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. Methods: PBMC collected from 67 participants were screened by IFNγ ELISPOT response to Tp sonicate. Tp -reactive T cell lines from blood and skin were probed for responses to 88 recombinant Tp antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. Results: We detected CD4+ T cell responses to Tp sonicate ex vivo. Using Tp -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. Conclusions: Tp infection 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. The Tp antigenic targets we identified may be high priority vaccine candidates.

College students' virtual and in-person drinking contexts during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in pronounced changes for college students, including shifts in living situations and engagement in virtual environments. Although college drinking decreased at the onset of the pandemic, a nuanced understanding of pandemic-related changes in drinking contexts and the risks conferred by each context on alcohol use and related consequences have yet to be assessed. METHODS: Secondary data analyses were conducted on screening data from a large parent clinical trial assessing a college student drinking intervention (N = 1669). Participants across six cohorts (from Spring 2020 to Summer 2021) reported on the frequency of drinking in each context (i.e., outside the home, home alone, home with others in-person, and home with others virtually), typical amount of drinking, and seven alcohol-related consequence subscales. RESULTS: Descriptive statistics and negative binomial regressions indicated that the proportion and frequency of drinking at home virtually with others decreased, while drinking outside the home increased from Spring 2020 to Summer 2021. Limited differences were observed in the proportion or frequency of individuals drinking at home alone or at home with others in-person. Negative binomial and logistic regressions indicated that the frequency of drinking outside the home was most consistently associated with more alcohol-related consequences (i.e., six of the seven subscales). However, drinking at home was not without risks; drinking home alone was associated with abuse/dependence, personal, social, hangover, and social media consequences; drinking home with others virtually was associated with abuse/dependence and social consequences; drinking home with others in-person was associated with drunk texting/dialing. CONCLUSION: The proportion and frequency of drinking in certain contexts changed during the COVID-19 pandemic, although drinking outside the home represented the highest risk drinking context across the pandemic. Future prevention and intervention efforts may benefit from considering approaches specific to different drinking contexts.