Pawelec G, Rehbein A, Katrilaka K, Balko I, Busch F W
Immunology Laboratory, 2nd Department of Internal Medicine, University Medical Clinic, Tübingen, F.R.G.
Immunopharmacology. 1988 Nov-Dec;16(3):207-16. doi: 10.1016/0162-3109(88)90009-4.
Cyclosporin A (CsA) blocks stimulation and growth of alloreactive T helper cell clones (Th-TCC), even in the presence of exogenous Interleukin-2 (IL-2). To examine whether this might reflect a generalised inhibition of cytokine production by these cells, their production of granulocyte/macrophage colony-stimulating factors (GM-CSF), thought not to be involved in the autocrine proliferation of the clones themselves, was investigated. Contrary to the prediction that only pathways relevant to T cell clonal expansion would be blocked by CsA, it was found that this immunosuppressive substance exerted a profound inhibitory activity on GM-CSF secretion, even in the presence of exogenous IL-2. Although a higher concentration of CsA was required to block GM-CSF secretion than to block proliferation, the former was not due to toxic effects on the cells, or permanently switching off the genes for GM-CSF, since upon further cultivation of the clones without CsA, alloantigen-specific responsiveness was restored. These results therefore show that clonal human T helper cell populations are sensitive to inhibition of GM-CSF secretion by CsA. Part of the immunosuppressive mechanism of action of CsA may therefore reside in this activity, since blockade of GM-CSF secretion by T helper cells would influence functional activities of antigen presenting cells.
环孢菌素A（CsA）可阻断同种反应性T辅助细胞克隆（Th-TCC）的刺激和生长，即使在外源白细胞介素-2（IL-2）存在的情况下也是如此。为了研究这是否可能反映这些细胞对细胞因子产生的普遍抑制，研究了它们对粒细胞/巨噬细胞集落刺激因子（GM-CSF）的产生，认为该因子与克隆自身的自分泌增殖无关。与仅与T细胞克隆扩增相关的途径会被CsA阻断的预测相反，发现这种免疫抑制物质对GM-CSF分泌具有深远的抑制活性，即使在外源IL-2存在的情况下也是如此。虽然阻断GM-CSF分泌所需的CsA浓度高于阻断增殖所需的浓度，但前者并非由于对细胞的毒性作用或永久关闭GM-CSF基因，因为在无CsA的情况下进一步培养克隆后，同种抗原特异性反应性得以恢复。因此，这些结果表明克隆性人T辅助细胞群体对CsA抑制GM-CSF分泌敏感。因此，CsA免疫抑制作用机制的一部分可能在于这种活性，因为T辅助细胞对GM-CSF分泌的阻断会影响抗原呈递细胞的功能活性。
