Effects of cyclosporin A on functions of specific murine T cell clones: inhibition of proliferation, lymphokine secretion and cytotoxicity |
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| Authors: | J Weiss B Schwinzer H Kirchner D Gemsa K Resch |
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| Institution: | 1. Division of Molecular Pharmacology, Department of Pharmacology and Toxicology, Medical School Hannover;2. Institute for Virus Research, German Cancer Research Center, Heidelberg, Federal Republic of Germany;1. College of Electrical, Energy and Power Engineering, YangZhou University, Yangzhou, Jiangsu 225127, PR China;2. Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing, Jiangsu 210096, PR China;3. Jiangsu Key Laboratory of Micro and Nano Heat Fluid Flow Technology and Energy Application, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou, Jiangsu 215009, PR China;1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;2. Guangdong Provincial Key Laboratory of Chiral Molecules and Drug Discovery, Sun Yat-sen University, Guangzhou 510006, China;3. The First Affiliated Hospital of Guangxi Medical University, Guangxi 530000, China;1. Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain;2. Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), 66123 Saarbrücken, Germany;3. Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany;4. Department of Pharmacology. University of Valencia, Valencia, Spain |
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| Abstract: | Allospecific T lymphocyte clones with different functions were generated from spleen cells of C 57/Bl6 mice following sensitization in vitro by a one-way mixed lymphocyte culture (MLC) with irradiated DBA/2 spleen cells. The clones were propagated in vitro in the presence of interleukin 2 (IL 2) and restimulation with stimulator cells. In these clones Cyclosporin A (CSA) was tested for its suppressive effect on different T lymphocyte functions. The antigen-dependent proliferation of a helper clone (HTL) was totally inhibited by 50 ng/ml CSA. Proliferation induced by simultaneous administration of antigen and IL 2 was partially suppressed in all helper and cytotoxic clones (CTL). The IL 2-driven proliferation in the absence of antigen was also suppressed between 25-70% by the immunosuppressive drug. Secretion of macrophage activating factor (MAF) and interferon (IFN) by HTL and CTL in response to antigen or mitogen was reduced dose dependently by CSA. Concentrations of 50 ng/ml CSA diminished lymphokine secretion to approximately 10% of controls, also when excess IL 2 was present. Cytotoxicity, previously described to be insensitive to the drug, could be suppressed by 50 ng/ml CSA to a various extent, from 40-70%, in different cytotoxic clones when the effector cells were preincubated with CSA for 1 h or more. Conclusively, the data suggest that CSA interferes generally with the activation of T lymphocyte clones. |
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