Suppression by cyclosporin A of murine T-cell-mediated immunity against viruses in vivo and in vitro |
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Authors: | A W Huegin A Cerny H Hengartner R M Zinkernagel |
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Affiliation: | 1. LB3, Faculty of Exact Science and Engineering, University of Madeira, 9020-105 Funchal, Portugal;2. CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Porto, Portugal;3. Department of Biosystems, Faculty of New Technologies Engineering, Shahid Beheshti University, Evin, P.O. Box 19839-4716, Tehran, Iran;1. State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001, PR China;2. National Energy Center for Coal to Liquids, Synfuels China Co., Ltd., Huairou District, Beijing 101400, PR China;3. University of Chinese Academy of Sciences, Beijing 100049, PR China |
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Abstract: | The immunosuppressive effect of Cyclosporin A on T-cell-mediated antiviral immune responses was examined. When administered intraperitoneally CS-A abrogated anti-vaccinia virus, anti-lymphocytic choriomeningitis virus (LCMV), and anti-vesicular stomatitis virus (VSV) T-cell responses in a dose-dependent fashion. Usually 50-60 mg/kg were efficient in suppressing primary T-cell responses completely. In contrast, 10-20 mg/kg often enhanced T-cell responses significantly when compared with controls. Suppression was observed if CS-A treatment was started before virus injection and up to 12 hr after infection; CS-A given 24 hr after the virus still suppressed T-cell activity partially. A 50 mg/kg dose of CS-A suppressed secondary anti-vaccinia virus or anti-VSV T-cell responses in vivo by a factor of about 10. This dose suppressed the primary T-cell-dependent footpad swelling induced by local LCMV infection and prevented T-cell-mediated immunopathological death due to LCM when LCMV was injected intracerebrally. In addition, clearance of LCMV was delayed drastically by CS-A treatment. When added to cultures of in vivo-primed antiviral T cells that were restimulated in vitro, CS-A inhibited both proliferation as well as generation of virus-specific cytotoxic T cells in a dose-dependent way. The results show that in CS-A-treated mice primary and secondary antiviral T-cell responses are strongly inhibited; acute viral infections with cytopathic viruses may therefore be more dramatic. In contrast immunopathological T-cell-mediated disease caused by noncytopathic viruses such as LCMV may be prevented or attenuated. |
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