Activation-induced expression of CD56 by T cells is associated with a reprogramming of cytolytic activity and cytokine secretion profile in vitro

Abstract

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-gamma (IFN-gamma) 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-gamma, 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.