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正常马和感染马传染性贫血病毒的马中皮质类固醇免疫抑制及单克隆抗体介导的CD5⁺ T淋巴细胞耗竭

Corticosteroid immunosuppression and monoclonal antibody-mediated CD5+ T lymphocyte depletion in normal and equine infectious anaemia virus-carrier horses.

作者信息

Tumas D B, Hines M T, Perryman L E, Davis W C, McGuire T C

机构信息

Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman 99164-7040.

出版信息

J Gen Virol. 1994 May;75 ( Pt 5):959-68. doi: 10.1099/0022-1317-75-5-959.

DOI:10.1099/0022-1317-75-5-959
PMID:7513746
Abstract

The immune control of chronic equine infectious anaemia (EIA) lentiviral infection was investigated by specifically depleting CD5+ T lymphocytes in vivo with monoclonal antibody (MAb) or by immunosuppression with corticosteroids. MAb was given at 25 to 50 mg/day intravenously for 11 days. Murine IgG1 anti-equine CD2 MAb (n = 2 horses) or IgG1 (n = 2) and IgG2a control MAb (n = 2 normal; 2 EIA-infected) did not deplete CD2+ T lymphocytes in horses. Horses given murine IgG2a anti-CD5 MAb HB19A (n = 4 normal; 5 EIA-infected) had depletion of peripheral blood CD5+ T lymphocytes during treatment. These horses, however, maintained a residual population of CD2+ T lymphocytes [15 (+/- 3)% of pretreatment numbers] that did not express CD5 but expressed either CD4 or CD8. These antigenically modulated CD5- T lymphocytes responded normally in vivo to intradermal inoculation with phytohaemagglutinin and in vitro to allogeneic leukocyte stimulation in one-way mixed lymphocyte reactions. EIA virus-infected horses (n = 5) did not develop recrudescent viraemia or disease following in vivo CD5+ T lymphocyte depletion. Immunosuppression of EIA virus-infected horses with corticosteroids (1 mg/kg body weight/day, intravenously for 9 days) resulted in detectable recrudescent EIA viraemia in 6/11 horses (55%) and recrudescent disease in 9/11 horses (82%). Normal horses (n = 3) treated with corticosteroids developed no clinical disease. These results demonstrate that the use of murine IgG2a MAbs to appropriate equine lymphocyte antigens will facilitate in vivo investigation of the role of T lymphocyte subpopulations in the control of EIA or other important equine diseases.

摘要

通过用单克隆抗体(MAb)在体内特异性清除CD5⁺ T淋巴细胞或用皮质类固醇进行免疫抑制,研究了慢性马传染性贫血(EIA)慢病毒感染的免疫控制情况。MAb以25至50毫克/天的剂量静脉注射,持续11天。鼠IgG1抗马CD2 MAb(n = 2匹马)或IgG1(n = 2)以及IgG2a对照MAb(n = 2匹正常马;2匹EIA感染马)并未清除马体内的CD2⁺ T淋巴细胞。给予鼠IgG2a抗CD5 MAb HB19A的马(n = 4匹正常马;5匹EIA感染马)在治疗期间外周血CD5⁺ T淋巴细胞减少。然而,这些马维持了一群残留的CD2⁺ T淋巴细胞[占治疗前数量的15(±3)%],这些细胞不表达CD5,但表达CD4或CD8。这些抗原性调节的CD5⁻ T淋巴细胞在体内对皮内接种植物血凝素反应正常,在体外对单向混合淋巴细胞反应中的同种异体白细胞刺激反应也正常。体内CD5⁺ T淋巴细胞耗竭后,EIA病毒感染的马(n = 5)未出现病毒血症复发或疾病。用皮质类固醇对EIA病毒感染的马进行免疫抑制(1毫克/千克体重/天,静脉注射9天),导致11匹马中有6匹(55%)出现可检测到的EIA病毒血症复发,11匹马中有9匹(82%)出现疾病复发。用皮质类固醇治疗的正常马(n = 3)未出现临床疾病。这些结果表明,使用针对合适马淋巴细胞抗原的鼠IgG2a MAb将有助于在体内研究T淋巴细胞亚群在控制EIA或其他重要马病中的作用。

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