Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment.
Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment.
复制标题
小牛功能性 CD4 T 淋巴细胞的长期体内耗竭需要胸腺切除术和抗 CD4 单克隆抗体治疗。
DOI：
10.1046/j.1365-2567.2001.01211.x
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发表时间：
2001
期刊：
影响因子：
6.4
通讯作者：
Knowles,DP
中科院分区：
文献类型：
--
作者：
Valdez,RA;McGuire,TC;Brown,WC;Davis,WC;Knowles,DP
淋巴细胞亚群的体内耗竭是用于剖析保护性免疫机制的直接方法。仅用单克隆抗体 (mAb) 治疗很难实现牛 T 淋巴细胞亚群的长期体内耗竭。本研究的目的是确定胸腺切除术和抗 CD4 mAb 治疗是否可以优化功能性牛 CD4+T 淋巴细胞的长期体内耗竭。小牛被切除胸腺，并用高剂量的抗 CD4 mAb（约 5 mg/kg）治疗 4 天以上，随后每周两次施用较低剂量（约 0·3mg/kg），持续 7 周。与胸腺完整的抗 CD4 mAb 处理的犊牛相比，胸腺切除的犊牛血液、脾脏和周围淋巴结中 CD4+T 淋巴细胞的消耗显着改善。在为期 8 周的研究期间，胸腺切除和胸腺完整的小牛之间的 CD4+T 淋巴细胞百分比存在显着差异。来自胸腺切除的小牛的 CD4+T 淋巴细胞的耗竭导致对卵清蛋白的淋巴增殖反应完全消除。此外，与胸腺完整的抗 CD4 mAb 处理的小牛相比，用抗 CD4 mAb 处理的胸腺切除小牛的免疫球蛋白 G1 显着降低，且未检测到免疫球蛋白 G2 卵清蛋白特异性抗体反应。本研究的结果表明，胸腺切除术和抗 CD4 mAb 治疗都是长期体内消耗功能性牛 CD4+T 淋巴细胞所必需的。
In vivodepletion of lymphocyte subsets is a direct approach used for dissection of the mechanisms of protective immunity. Long‐termin vivodepletion of bovine T lymphocyte subpopulations with monoclonal antibody (mAb) treatment alone has been difficult to achieve. The objective of this study was to determine whether both thymectomy and anti‐CD4 mAb treatment would optimize long‐termin vivodepletion of functional bovine CD4+T lymphocytes. Calves were thymectomized and treated with high doses of anti‐CD4 mAb (approximately 5 mg/kg) over 4 days followed by subsequent lower doses (approximately 0·3 mg/kg) administered twice weekly for an additional 7 weeks. Depletion of CD4+T lymphocytes from blood, spleen and peripheral lymph nodes was significantly improved in thymectomized calves compared to thymus‐intact anti‐CD4 mAb‐treated calves. Significant differences in percentages of CD4+T lymphocytes between thymectomized and thymus‐intact calves were sustained for the duration of the 8‐week study. Depletion of CD4+T lymphocytes from thymectomized calves resulted in complete abrogation of lymphoproliferative responses to ovalbumin. In addition, thymectomized calves treated with anti‐CD4 mAb had significantly reduced immunoglobulin G1 and no detectable immunoglobulin G2 ovalbumin‐specific antibody responses compared to thymus‐intact anti‐CD4 mAb‐treated calves. The results of this study demonstrate that both thymectomy and treatment with anti‐CD4 mAb are required for long‐termin vivodepletion of functional bovine CD4+T lymphocytes.