Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rgammanull mice.
Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rgammanull mice.
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DOI：
10.1016/j.humimm.2010.02.019
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发表时间：
2010-06
期刊：
影响因子：
2.7
通讯作者：
Burlingham WJ
中科院分区：
文献类型：
--
作者：
Rajesh D;Zhou Y;Jankowska-Gan E;Roenneburg DA;Dart ML;Torrealba J;Burlingham WJ
我们在携带人胸腺类器官的人源化NOD-scid IL 2 r-γ-null（Hu-NSG）小鼠中评估了用同基因人白细胞进行多线移植重建后人T细胞的免疫活性。通过免疫的hu-NSG宿主的直接足垫攻击或通过将来自免疫的hu-NSG的脾细胞与抗原一起沿着转移到CB 17 SCID小鼠的足垫中[trans-vivo（tv）DTH]来评估迟发型超敏反应（DTH）应答。两种方法均显示对破伤风类毒素（TT）或V型胶原（ColV）的细胞免疫。肿胀足垫的免疫组织化学分析显示人CD 45+细胞浸润，包括CD 3 + T细胞、CD 68+巨噬细胞和鼠Ly 6 G+中性粒细胞。我们观察到%循环人CD 4+细胞和直接DTH肿胀反应TT之间的显着相关性。对TT的tvDTH应答被抗IFN γ抑制，而对胶原V的tvDTH应答被抗IL-17抗体抑制，模拟成人T细胞对这些抗原的细胞因子偏好。Hu-NSG小鼠还能够对TT抗原产生B细胞反应（主要是IgM）。Th 1或Th 17依赖性细胞免疫应答的激活支持Hu-NSG小鼠作为同种异体移植排斥和自身免疫的替代模型的效用。
We evaluated the immunocompetence of human T cells in humanized NOD-scid IL2r-γ-null (Hu—NSG) mice bearing a human thymic organoid, after multilinegage reconstitution with isogeneic human leukocytes. Delayed type hypersensitivity (DTH) response was assessed by a direct footpad challenge of the immunized hu-NSG host, or by transfer of splenocytes from immunized hu-NSG, along with antigen, into footpads of CB17 SCID mice [trans-vivo (tv) DTH]. Both methods revealed cellular immunity to tetanus toxoid (TT) or collagen type V (ColV). Immunohistochemical analysis of the swollen footpads revealed infiltration of human CD45+ cells, including CD3+ T cells, CD68+ macrophages and murine Ly6G+ neutrophils. We observed a significant correlation between % circulating human CD4+ cells and the direct DTH swelling response to TT. The tvDTH response to TT was inhibited by anti-IFNγ, while the tvDTH response to collagen V was inhibited by anti IL-17 antibody, mimicking the cytokine bias of adult human T cells to these antigens. Hu-NSG mice were also capable of mounting a B cell response (primarily IgM) to TT antigen. The activation of either Th1- or Th17 - dependent cellular immune response supports the utility of Hu-NSG mice as a surrogate model of allograft rejection and autoimmunity.
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1164/rccm.200612-1901oc
发表时间：
2008-03-15
影响因子：
24.7
作者：
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通讯作者：
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影响因子：
6.4
作者：
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通讯作者：
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