THE C-KIT LIGAND POTENTIATES THE ALLOGENEIC MIXED LYMPHOCYTE-REACTION

The allogeneic mixed lymphocyte reaction (MLR) is a complex in vitro a ssay of T-cell recognition and responsiveness in which interleukin-2 ( IL-2) plays a central role. We have previously demonstrated that c-kit ligand (KL) can enhance IL-2-induced proliferation in a subset of hum an natural killer cells expressing the c-kit tyrosine kinase receptor. In the present study, we asked whether KL could enhance IL-2-mediated T-cell proliferation in the allogeneic MLR. We demonstrate that the v ast majority of activated human T-cell clones express the c-kit mRNA t ranscript. Binding studies performed on activated T cells with radioio dinated KL were consistent with the expression of a single class of c- hit receptors. The addition of exogenous KL to the MLR led to an incre ase in tritiated thymidine ((3)[H]-TdR) incorporation in the absence o f other exogenous cytokines, and did so in a dose-dependent fashion. A reproducible increase in (3)[H]-TdR incorporation was noted at concen trations of KL, which approximate those normally found in vivo. Antibo dy blocking of KL binding to c-kit, T-cell depletion and sorting exper iments suggest that the action of KL is mediated at least in part by a direct effect on both CD4(+) and CD8(+) T-cells. KL's enhancement of the MLR also requires the binding of IL-2 to its high-affinity IL-2 re ceptor. Given the abundance of KL normally found in human serum, these data suggest that this cytokine may have a role during T-cell activat ion in vivo. (C) 1996 by The American Society of Hematology.