Expression of CD38 Regulates Proliferative Capacity and Immunosuppressive Function of Regulatory T Cells In Vitro

Abstract

Background:
Regulatory T cells (Tregs) play a pivotal role in maintaining immunological tolerance. Although CD38 possesses NAD+ nucleosidase activity and regulates calcium signaling, its specific contribution to Treg biology remains to be fully elucidated.
Objectives: To investigate the effect of CD38 expression on the functional activity, proliferative potential, and suppressive capacity of regulatory T cells in vitro.
Materials and methods: CD4⁺CD25⁺FoxP3⁺ T cells were isolated from peripheral blood mononuclear cells of healthy donors using magnetic-activated cell sorting. CD38 expression was quantified by flow cytometry. Proliferative capacity (CFSE dilution assay) and effector T cell (Teff) suppression were compared between CD38^high and CD38^low Treg subsets.
Results: The CD38^high Treg subset constituted 24.5 ± 4.2% of total regulatory T cells. Compared with CD38^low Tregs, CD38^high Tregs exhibited significantly higher expression of FoxP3, CTLA-4, and ICOS (p < 0.001). In functional co-culture assays, CD38^high Tregs suppressed autologous Teff proliferation by 82.4%, whereas CD38^low Tregs achieved only 51.2% suppression (p < 0.001). Pharmacological inhibition of CD38 enzymatic activity significantly reduced IL-10 and TGF-β1 secretion.
Conclusions: CD38 expression serves as a marker for a hyperactivated regulatory T cell subset characterized by enhanced proliferative capacity and superior immunosuppressive potential.

Keywords:
CD38; regulatory T cells; Treg; FoxP3; immune tolerance; immunosuppression.