The c-kit ligand potentiates the allogeneic mixed lymphocyte reaction
EM Bluman, GS Schnier, BR Avalos, MP Strout, H Sultan, FW Jacobson, DE Williams, WE Carson and MA Caligiuri
Department of Hematologic Oncology and Bone Marrow Transplantation, Roswell
Park Cancer Institute, Buffalo, NY 14263, USA.
The allogeneic mixed lymphocyte reaction (MLR) is a complex in vitro assay
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 human 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 vast majority
of activated human T-cell clones express the c-kit mRNA transcript. Binding
studies performed on activated T cells with radioiodinated KL were
consistent with the expression of a single class of c-kit receptors. The
addition of exogenous KL to the MLR led to an increase in tritiated
thymidine (3[H]-TdR) incorporation in the absence of other exogenous
cytokines, and did so in a dose-dependent fashion. A reproducible increase
in 3[H]-TdR incorporation was noted at concentrations of KL, which
approximate those normally found in vivo. Antibody blocking of KL binding
to c-kit, T-cell depletion and sorting experiments 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 receptor. Given the abundance of KL normally found
in human serum, these data suggest that this cytokine may have a role
during T-cell activation in vivo.
Volume 88,
Issue 10,
pp. 3887-3893,
11/15/1996
Copyright © 1996 by The American Society of Hematology
