1. The tetraspanin CD151 marks a unique population of activated human T cells.
- Author
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Perez MD, Seu L, Lowman KE, Moylan DC, Tidwell C, Samuel S, Duverger A, Wagner FH, Carlin E, Sharma V, Pope B, Raman C, Erdmann N, Locke J, Hu H, Sabbaj S, and Kutsch O
- Subjects
- Adult, Aged, Case-Control Studies, Granzymes metabolism, HIV Seronegativity, HIV Seropositivity metabolism, Humans, Lymphocyte Activation, MAP Kinase Signaling System, Middle Aged, Spleen immunology, T-Lymphocytes cytology, CD3 Complex metabolism, HIV Seropositivity immunology, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes immunology, Tetraspanin 24 metabolism, Up-Regulation
- Abstract
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.
- Published
- 2020
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