Role of CD47 in the induction of human naive T cell anergy

We recently reported that CD47 ligation inhibited IL-2 release by umbilical cord blood mononuclear cells activated in the presence of IL-12, but not I L-4, preventing the induction of IL-12R beta (2) expression and the acquisi tion of Th1, but not the Th2 phenotype. Here we show that in the absence of exogenous cytokine at priming, CD47 ligation of umbilical cord blood monon uclear cells promotes the development of hyporesponsive T cells. Naive cell s were treated with CD47 mAb for 3 days, expanded in IL-2 for 9-12 days, an d restimulated by CD3 and CD28 coengagement. Effector T cells generated und er these conditions were considered to be anergic because they produced a r educed amount of IL-2 at the single-cell level and displayed an impaired ca pacity 1) to proliferate, 2) to secrete Th1/Th2 cytokines, and 3) to respon d to IL-2, IL-4, or IL-12. Moreover, CD47 mAb strongly suppressed IL-2 prod uction and IL-2R alpha expression in primary cultures and IL-2 response of activated naive T cells. Induction of anergy by CD47 mAb was IL-10 independ ent, whereas inclusion of IL-2 and IL-4, but not IL-7, at priming fully res tored T cell activation. Furthermore, CD28 costimulation prevented inductio n of anergy. Thus, CD47 may represent a potential target to induce anergy a nd prevent undesired Th0/Th1 responses such as graft vs host diseases, allo graft rejection, or autoimmune diseases.