The c-kit ligand potentiates the allogeneic mixed lymphocyte reaction
The c-kit ligand potentiates the allogeneic mixed lymphocyte reaction
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DOI：
10.1182/blood.v88.10.3887.bloodjournal88103887
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发表时间：
1996-11-15
期刊：
影响因子：
20.3
通讯作者：
Caligiuri, MA
中科院分区：
文献类型：
--
作者：
Bluman, EM;Schnier, GS;Caligiuri, MA
同种异体混合淋巴细胞反应（MLR）是一种复杂的体外T细胞识别和反应性试验，其中白细胞介素-2（IL-2）起着核心作用。我们以前已经证明，c-kit配体（KL）可以增强IL-2诱导的增殖在一个子集的人自然杀伤细胞表达c-kit酪氨酸激酶受体。在本研究中，我们问KL是否可以增强IL-2介导的T细胞增殖在同种异体MLR。我们证明，绝大多数活化的人T细胞克隆表达c-kit mRNA转录。对具有放射性碘标记的KL的活化T细胞进行的结合研究与单一类别的c-hit受体的表达一致。在不存在其他外源性细胞因子的情况下，将外源性KL添加到MLR中导致氚化胸苷（（3）[H]-TdR）掺入增加，并且以剂量依赖性方式增加。在KL浓度下，[H]-TdR掺入可重复增加，接近体内正常发现的浓度。抗体阻断KL与c-kit结合、T细胞耗竭和分选实验表明，KL的作用至少部分是通过对CD 4（+）和CD 8（+）T细胞的直接作用介导的。KL对MLR的增强还需要IL-2与其高亲和力IL-2受体的结合。鉴于KL通常在人血清中发现的丰度，这些数据表明，这种细胞因子可能在体内T细胞活化过程中发挥作用。(C)1996年，美国血液学会。
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-hit 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. (C) 1996 by The American Society of Hematology.