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*
Allergy Research Laboratory, Research Center of Centre Hospitalier Université de Montréal, Notre Dame Hospital, and
Department of Obstetrics and Gynecology, University of Montreal, Quebec, Canada
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 IL-4, preventing the induction of IL-12R
2
expression and the acquisition 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 mononuclear cells promotes the
development of hyporesponsive T cells. Naive cells were treated with
CD47 mAb for 3 days, expanded in IL-2 for 9–12 days, and restimulated
by CD3 and CD28 coengagement. Effector T cells generated under these
conditions were considered to be anergic because they produced a
reduced amount of IL-2 at the single-cell level and displayed an
impaired capacity 1) to proliferate, 2) to secrete Th1/Th2 cytokines,
and 3) to respond to IL-2, IL-4, or IL-12. Moreover, CD47 mAb strongly
suppressed IL-2 production and IL-2R
expression in primary cultures
and IL-2 response of activated naive T cells. Induction of anergy by
CD47 mAb was IL-10 independent, whereas inclusion of IL-2 and IL-4, but
not IL-7, at priming fully restored T cell activation. Furthermore,
CD28 costimulation prevented induction of anergy. Thus, CD47 may
represent a potential target to induce anergy and prevent undesired
Th0/Th1 responses such as graft vs host diseases, allograft rejection,
or autoimmune diseases.
This article has been cited by other articles:
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