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-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.
Kelly-Rogers
Jane
J
Lymphocyte Biology Group, Institute of Immunology and Department of Biology, The National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
Madrigal-Estebas
Laura
L
O'Connor
Tony
T
Doherty
Derek G
DG
D017252:CD3 Complex / Q000276:immunology; D019002:CD56 Antigen / Q000096:biosynthesis / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D017252:CD3 Complex; D019002:CD56 Antigen; D016207:Cytokines; D018793:Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma