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Tetraspanins are a family of proteins with an array of functions that are well studied in cancer biology, but their importance in immunology is underappreciated. Here we establish the tetraspanin CD151 as a unique marker of T-cell activation and, in extension, an indicator of elevated, systemic T-cell activity. Baseline CD151 expression found on a subset of T-cells was indicative of increased activation of the MAPK pathway. Following TCR/CD3 activation, CD151 expression was upregulated on the overall T-cell population, a quintessential feature of an activation marker. CD151+ T-cell frequencies in the spleen, an organ with increased immune activity, were twice as high as in paired peripheral blood samples. This CD151+ T-cell frequency increase was not paralleled by an increase of CD25 or CD38, demonstrating that CD151 expression is regulated independently of other T-cell activation markers. CD151+ T-cells were also more likely to express preformed granzyme B, suggesting that CD151+ T cells are pro-inflammatory. To this end, HIV-1 patients on antiretroviral therapy who are reported to exhibit chronically elevated levels of immune activity, had significantly higher CD4+CD151+ T-cell frequencies than healthy controls, raising the possibility that proinflammatory CD151+ T cells could contribute to the premature immunological aging phenotype observed in these patients.

Background: Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT)., Methods: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103 + CD69 + CD4 + and CD8 + T cells in mucosa-derived T cells from healthy and HIV-positive women., Results: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women. The expression of the mucosal retention receptor, CD103, from HIV-positive women was reduced compared to healthy women and was lowest in women with CD4 counts < 500 cells/mm 3 . Furthermore, CD103 expression on mucosa-derived CD8 + T cells correlated with antigen-specific IFN-γ production by mucosal CD4 + T cells and was inversely correlated with T-bet from CD8 + CD103 + mucosa-derived T cells., Conclusions: These data suggest that CD4 + T cells, known to be impaired during HIV-1 infection and necessary for the expression of CD103 in murine models, may play a role in the expression of CD103 on resident T cells from the human FGT., Competing Interests: The authors have no competing financial interests.