Trucco M, Shaw S, Korngold R
J Clin Invest. 1985 Sep;76(3):1032-41. doi: 10.1172/JCI112056.
We recently reported the biological activity and some of the biochemical characteristics of a factor produced by a human T cell hybrid clone able to block hematopoietic progenitor cell proliferation. This 85-kD protein factor, which we have termed colony-inhibiting lymphokine (CIL), has growth regulatory activity on bone marrow precursors bearing Ia (class II) antigens of either granulocytic-monocytic (CFU-GM) or erythroid lineage (BFU-E and CFU-E). Experiments aimed to investigate the specificity of the inhibitory effect on hematopoietic progenitor cell growth suggested that the expression of HLA-DR surface antigens was required on the target cells. We describe in this communication how DR+ cell lines ceased dividing after a few days of culture in the presence of CIL, whereas DR- cell lines were completely unaffected. The increased DR expression on the ML3 cell surface, mediated by the activity of the gamma interferon (IFN gamma), increases the sensitivity to the growth inhibition factor of the ML3 cell line. To verify the hypothesis that the DR antigens might serve as receptors for the factor, enabling it also to interfere in the immune response, we tested CIL in a mixed lymphocyte reaction (MLR), one of the best known in vitro Ia antigen-dependent T cell-mediated immune responses. CIL is able to block major histocompatibility complex-allogeneic MLR both in human and mouse systems. The data indicate that CIL recognizes a nonpolymorphic structure (presumably on all Ia molecules) presented by stimulator cells of either species, and thereby interferes with specific interactions between stimulator and responder cells. Blocking of the alloantigen stimulation stage is also indicated, since CIL is effective only if added to the culture medium during the first 48 h of the MLR. Finally, mouse monoclonal anti-DR antibodies are able to sharply reduce CIL activity on sensitive DR+ cell lines. CIL may act physiologically as a multifunctional mediator in a complex network that links regulation of bone marrow differentiation and the generation of immune responses.
我们最近报道了一种由人T细胞杂交克隆产生的因子的生物学活性和一些生化特性，该因子能够阻断造血祖细胞增殖。这种85-kD的蛋白质因子，我们称之为集落抑制淋巴因子（CIL），对带有Ia（II类）抗原的骨髓前体细胞具有生长调节活性，这些前体细胞来自粒细胞-单核细胞系（CFU-GM）或红系（BFU-E和CFU-E）。旨在研究对造血祖细胞生长抑制作用特异性的实验表明，靶细胞上需要表达HLA-DR表面抗原。我们在本通讯中描述了DR +细胞系在CIL存在下培养几天后如何停止分裂，而DR-细胞系则完全不受影响。由γ干扰素（IFNγ）的活性介导的ML3细胞表面DR表达的增加，增加了ML3细胞系对生长抑制因子的敏感性。为了验证DR抗原可能作为该因子的受体，使其也能干扰免疫反应这一假设，我们在混合淋巴细胞反应（MLR）中测试了CIL，MLR是最著名的体外Ia抗原依赖性T细胞介导的免疫反应之一。CIL能够在人和小鼠系统中阻断主要组织相容性复合体-同种异体MLR。数据表明，CIL识别两种物种的刺激细胞呈现的非多态性结构（可能在所有Ia分子上），从而干扰刺激细胞和应答细胞之间的特异性相互作用。还表明阻断了同种异体抗原刺激阶段，因为CIL仅在MLR的前48小时添加到培养基中才有效。最后，小鼠单克隆抗DR抗体能够大幅降低CIL对敏感DR +细胞系的活性。CIL可能在生理上作为一个复杂网络中的多功能介质，该网络将骨髓分化的调节与免疫反应的产生联系起来。
