Dessureault S, Shpitz B, Alloo J, Rotstein O, Sandhu J, Hozumi N, Fernandes B, Gallinger S
Department of Surgery, Samuel Lunenfeld Research Institute, and Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Transplantation. 1997 Sep 27;64(6):811-6. doi: 10.1097/00007890-199709270-00004.
Our goal was to study physiologic responses of human T lymphocytes to OKT3 in the human peripheral blood lymphocyte-severe combined immunodeficiency (hu-PBL-SCID) mouse model.
SCID mice were pretreated with anti-asialo-GM1 (alpha-ASGM1) and radiation, then engrafted with human peripheral blood lymphocytes (PBLs). Seven to 14 days after engraftment, when most human T cells in the spleen of these mice are CD3+/CD4+ and CD3+/CD8+, mice were treated with OKT3 or control antibody. Mice were killed for histopathologic examination, for flow cytometric assessment of the engrafted human lymphocytes, and for analysis of human tumor necrosis factor-alpha serum levels.
Intravenous injection of 5 microg of OKT3 resulted in early antigenic modulation of engrafted human T lymphocytes, with the emergence of CD3-/CD4+ and CD3-/CD8+ cells in the spleen of hu-PBL-SCID mice. There was an increase in the serum concentration of human tumor necrosis factor-alpha within 4 hr after OKT3 injection, suggesting early T-cell activation. Antigenic modulation and activation of the human lymphocytes in the spleen was followed by their depletion within 24 hr. This human T-cell response to OKT3 in hu-PBL-SCID mice is analogous to the response in humans treated with OKT3 and in BALB/c mice injected with an anti-murine CD3 monoclonal antibody. Graft-versus-host disease in the mice was abrogated by OKT3 treatment, and OKT3-treated mice lived longer than controls. Histopathologic studies showed clearance of lymphocytic infiltration in the liver and lungs of OKT3-treated mice.
These findings provide further evidence of functional human immune T cells in the hu-PBL-SCID mouse. This model may have useful applications in the study of transplantation immunology.
我们的目标是在人外周血淋巴细胞 - 重症联合免疫缺陷（hu - PBL - SCID）小鼠模型中研究人T淋巴细胞对OKT3的生理反应。
先用抗去唾液酸GM1（α - ASGM1）和辐射预处理SCID小鼠，然后植入人外周血淋巴细胞（PBL）。植入后7至14天，当这些小鼠脾脏中的大多数人T细胞为CD3 + / CD4 +和CD3 + / CD8 +时，用OKT3或对照抗体处理小鼠。处死小鼠以进行组织病理学检查、对植入的人淋巴细胞进行流式细胞术评估以及分析人肿瘤坏死因子 - α血清水平。
静脉注射5μg OKT3导致植入的人T淋巴细胞早期抗原调节，hu - PBL - SCID小鼠脾脏中出现CD3 - / CD4 +和CD3 - / CD8 +细胞。OKT3注射后4小时内人肿瘤坏死因子 - α血清浓度升高，提示早期T细胞活化。脾脏中人淋巴细胞的抗原调节和活化之后在24小时内出现细胞耗竭。hu - PBL - SCID小鼠中这种人T细胞对OKT3的反应类似于接受OKT3治疗的人以及注射抗小鼠CD3单克隆抗体的BALB / c小鼠中的反应。OKT3治疗消除了小鼠中的移植物抗宿主病，且接受OKT3治疗的小鼠比对照存活时间更长。组织病理学研究显示OKT3治疗的小鼠肝脏和肺部淋巴细胞浸润清除。
这些发现为hu - PBL - SCID小鼠中功能性人免疫T细胞提供了进一步证据。该模型在移植免疫学研究中可能有有用的应用。
