TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
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DOI：
10.1172/jci23961
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发表时间：
2005-10-01
影响因子：
15.9
通讯作者：
Herold, KC
中科院分区：
文献类型：
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作者：
Bisikirska, B;Colgan, J;Herold, KC
修饰的抗 CD3 mAb 正在成为在移植和自身免疫（例如 1 型糖尿病）等环境中诱导免疫耐受的可能手段。在 1 型糖尿病患者中进行的改良抗 CD3 mAb [hOKT3 gamma 1(Ala-Ala)] 试验中，我们通过 mAb 治疗后外周血 CD8(+) 细胞数量的增加来确定临床反应者。在这里，我们发现抗CD3 mAb引起CD8（+）T细胞的激活（在体外和体内相似）并诱导调节性CD8（+）CD25（+）T细胞。这些细胞抑制 CD4(+) 细胞对 mAb 本身和抗原的反应。调节性CD8(+)CD25(+)细胞为CTLA4(+)和Foxp3(+)，需要接触才能抑制。 mAb 治疗期间患者的 CD8+ T 细胞上也诱导了 Foxp3，这表明抗 CD3 mAb 免疫调节作用的潜在机制涉及诱导调节性 CD8+ T 细胞子集。
Modified anti-CD3 mAbs are emerging as a possible means of inducing immunologic tolerance in settings including transplantation and autoimmunity such as in type 1 diabetes. In a trial of a modified anti-CD3 mAb [hOKT3 gamma 1(Ala-Ala)] in patients with type 1 diabetes, we identified clinical responders by an increase in the number of peripheral blood CD8(+) cells following treatment with the mAb. Here we show that the anti-CD3 mAb caused activation of CD8(+) T cells that was similar in vitro and in vivo and induced regulatory CD8(+)CD25(+) T cells. These cells inhibited the responses of CD4(+) cells to the mAb itself and to antigen. The regulatory CD8(+)CD25(+) cells were CTLA4(+) and Foxp3(+) and required contact for inhibition. Foxp3 was also induced on CD8(+) T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8(+) T cells.