A novel human CD4⁺ T-cell inducer subset with potent immunostimulatory properties

The complexity of immunoregulation has focused attention on the CD4 ⁺ T "suppressor" regulatory cell (T_reg), which helps maintain balance between immunity and tolerance. An immunoregulatory T-cell population that upon activation amplifies cellular immune responses was described in murine models more than 30 years ago; however, no study has yet identified a naturally occurring T "inducer" cell type. Here, we report that the ectoenzyme CD39/NTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase 1) helps to delineate a novel population of human "inducer" CD4⁺ T cells (T_ind) that significantly increases the proliferation and cytokine production of responder T cells in a dose-dependent manner. Furthermore, this unique T_ind subset produces a distinct repertoire of cytokines in comparison to the other CD4⁺ T-cell subsets.We propose that this novel CD4⁺ T-cell population counterbalances the suppressive activity of suppressor T_reg in peripheral blood and serves as a calibrator of immunoregulation.