Bisikirska Brygida, Colgan John, Luban Jeremy, Bluestone Jeffrey A, Herold Kevan C
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Clin Invest. 2005 Oct;115(10):2904-13. doi: 10.1172/JCI23961. Epub 2005 Sep 15.
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 [hOKT3gamma1(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.
改良抗CD3单克隆抗体正逐渐成为在包括移植和自身免疫性疾病（如1型糖尿病）等情况下诱导免疫耐受的一种可能手段。在一项针对1型糖尿病患者的改良抗CD3单克隆抗体[hOKT3γ1(Ala - Ala)]试验中，我们通过治疗后外周血CD8⁺细胞数量增加来确定临床反应者。在此我们表明，抗CD3单克隆抗体引起的CD8⁺T细胞激活在体外和体内相似，并诱导了调节性CD8⁺CD25⁺T细胞。这些细胞抑制了CD4⁺细胞对单克隆抗体本身及抗原的反应。调节性CD8⁺CD25⁺细胞表达CTLA4和Foxp3，且抑制作用需要细胞间接触。在单克隆抗体治疗期间，患者的CD8⁺T细胞也诱导表达了Foxp3，这提示抗CD3单克隆抗体免疫调节作用的一种潜在机制涉及诱导调节性CD8⁺T细胞亚群。
