Activation-Induced Expression of CD56 by T Cells Is Associated With a Reprogramming of Cytolytic Activity and Cytokine Secretion Profile In Vitro

A subset of human T lymphocytes expresses the natural killer (NK) cell-associated receptor CD56 and is capable of major histocompatibility complex (MHC)–unrestricted cytotoxicity against a variety of autologous and allogeneic tumor cells. CD56+ T cells have shown potential for immunotherapy as antitumor cytotoxic effectors, but their capacity to control adaptive immune responses via cytokine secretion is unclear. We have examined the inducibility of CD56+ T cells from human blood in vitro and compared the kinetics of Th1, Th2, and regulatory cytokine secretion by CD56+ T cells with those of conventional CD56− T cells. CD56 was induced on CD8+ and CD4−CD8− T cells by CD3/T-cell receptor (TCR)-mediated activation, particularly when grown in the presence of interleukin (IL)-2. Activation-induced CD56+ T cells proliferated less vigorously but displayed enhanced natural cytotoxicity compared with CD56− T cells. CD56+ T cells released interferon-γ (IFN-γ) and interleukin-13 (IL-13), but not IL-10, upon TCR stimulation. Flow cytometric analysis demonstrated that, compared with CD56− T cells, elevated proportions of CD56+ T cells expressed IFN-γ, IL-4, and IL-13 within hours of activation. These acquired cytolytic and cytokine secretion activities of CD56+ T cells make them potential targets for immunotherapy for infectious and immune-mediated disease.