Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody can prevent rat cardiac allograft rejection
Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody can prevent rat cardiac allograft rejection
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DOI：
10.1016/j.healun.2008.01.004
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发表时间：
2008-04-01
影响因子：
8.9
通讯作者：
Li, Xiao-Kang
中科院分区：
文献类型：
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作者：
Kitazawa, Yusuke;Fujino, Masayuki;Li, Xiao-Kang
背景资料：众所周知，CD 4（+）CD 25（+）调节性T（Treg）细胞在抑制自身免疫、炎症和同种异体移植物排斥中起中心作用。方法：本研究旨在观察超激动性CD 28特异性单克隆抗体对CD 28细胞亚群的作用，并探讨其对CD 28细胞亚群的抑制作用（supCD 28）单克隆抗体对大鼠自然产生的CD 4（+）CD 25（+）Treg（nTreg）细胞的优先扩增及其在心脏移植中的适用性。单次给予supCD 28 MAb优先增殖nTreg细胞。Foxp 3表达的增加和向Th 2细胞因子谱的极化与扩增的CD 4（+）CD 25（+）Treg亚群中干扰素-γ的产生减少和白细胞介素-4和-10的产生增加相关，其能够抑制纯化后的CD 4（+）CD 25（-）T细胞增殖。此外，supCD 28单克隆抗体给药显示nTreg细胞优先在体内增殖并募集到移植物中，导致完全MHC错配心脏移植物存活的显著延长。我们的数据表明，supCD 28 MAb靶向体内nTreg细胞的扩增，并维持和增强其调节功能，其代表了多克隆活化的Treg细胞作为治疗同种异体移植排斥的细胞疗法的治疗用途的主要进展。
Background: it is well known that CD4(+)CD25(+) regulatory T (Treg) cells play a central role in the suppression of autoimmunity, inflammation and allograft rejection. Therefore, therapeutic agents that capable of enhancing the number and.activity of this T-cell subset are highly desirable.Methods: The present study was designed to investigate the effects of superagonistic CD28-specific monoclonal antibody (supCD28 MAb) on preferentially expanded rat naturally occurring CD4(+)CD25(+) Treg (nTreg) cells and its applicability in cardiac transplantation.Results: A single administration of supCD28 MAb preferentially proliferated nTreg cells. The increase of Foxp3 expression and polarization toward a Th2 cytokine profile correlated with decreased production of interferon-gamma and increased production of interleukin-4 and -10 in the expanded CD4(+)CD25(+) Treg subset, which was capable of suppressing CD4(+)CD25(-) T-cell proliferation after purification. Furthermore, supCD28 MAb administration revealed that nTreg cells were preferentially proliferating in vivo and recruited into the grafts, resulting in significant prolongation of full MHC-mismatch cardiac graft survival.Conclusions: Our data demonstrate that supCD28 MAb targets expansion of nTreg cells in vivo and maintains and enhances their regulatory functions, which represents a major advance toward the therapeutic use of polyclonally activated Treg cells as cellular therapy for treatment of allograft rejection.