Superagonist CD28 Antibody Preferentially Expanded Foxp3-Expressing nTreg Cells and Prevented Graft-Versus-Host Diseases
Superagonist CD28 Antibody Preferentially Expanded Foxp3-Expressing nTreg Cells and Prevented Graft-Versus-Host Diseases
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DOI：
10.1177/096368970901805-619
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Takahara, Shiro
中科院分区：
文献类型：
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作者：
Kitazawa, Yusuke;Fujino, Masayuki;Takahara, Shiro
在各种实验性移植模型中，调节性淋巴细胞在预防器官特异性自身免疫性疾病以及诱导和维持耐受性方面发挥着关键作用。提高外周血中CD4(+)CD25(+)Treg细胞的数量和活性是治疗自身免疫和抑制同种异体反应的一个明显的目标。目前的研究表明，自然产生的CD4(+)CD25(+)Treg(NTreg)细胞在注射单一超激动型CD28特异性单抗(SupCD28 MAb)后，在3天内优先增殖到4倍。Foxp3分子的增加伴随着Th2细胞因子的极化，在扩大的Treg亚群中，干扰素-γ的产生减少，IL-4和IL-10的产生增加。在移植物抗宿主病(GvHD)模型中过继转移supCD28单抗扩增的细胞可有效抑制致死性。这些结果表明，这种治疗作用是通过体内nTreg细胞的扩增来实现的。综上所述，这些数据表明，supCD28-mAb可以在体内靶向nTreg细胞，并维持和增强其对治疗GvHD的强大调节功能。
Regulatory lymphocytes play a pivotal role in preventing organ-specific autoimmune disease and in induction and maintenance of tolerance in various experimental transplantation models. The enhancement of the number and activity of peripheral CD4(+)CD25(+) Treg cells is an obvious goal for the treatment of autoimmunity and for the suppression of alloreactions. The present study demonstrates that naturally occurring CD4(+)CD25(+) Treg (nTreg) cells preferentially proliferate to a fourfold increase within 3 days in response to the administration of a single superagonistic CD28-specific monoclonal antibody (supCD28 mAb). The appearance of increased Foxp3 molecules was accompanied with polarization toward a Th2 cytokine profile with decreased production of IFN-gamma and increased production of IL-4 and IL-10 in the expanded Treg subset. Adoptive transfer of supCD28 mAb-expanded cells in a graft-versus-host disease (GvHD) model induced a potent inhibition of lethality. These results suggest that this therapeutic effect is mediated by the in vivo expansion of nTreg cells. Taken together, these data demonstrate that supCD28-mAb may target nTreg cells in vivo and maintain and enhance their potent regulatory functions for the treatment GvHD.