The c-kit ligand potentiates the allogeneic mixed lymphocyte reaction.
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.
Department of Hematologic Oncology and Bone Marrow Transplantation, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
E M
EM
Bluman
G S
GS
Schnier
B R
BR
Avalos
M P
MP
Strout
H
H
Sultan
F W
FW
Jacobson
D E
DE
Williams
W E
WE
Carson
M A
MA
Caligiuri
D000818:Animals; D004261:DNA Replication; D006648:Histocompatibility; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000502:physiology; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000145:classification; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000502:physiology; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D007519:Isoantigens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit