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.