Utku Nalân, Heinemann Thomas, Milford Edgar L
GenPat77 AG, Robert Koch Platz 4, Berlin 10117, Germany.
Curr Opin Investig Drugs. 2007 May;8(5):401-10.
The membrane protein T-cell immune response cDNA 7 (TIRC7) is transiently expressed in subsets of lymphocytes following antigen stimulation. The importance of TIRC7 in immune activation is demonstrated by the effect of antibodies directed against extracellular domains of TIRC7. In vitro targeting of TIRC7 inhibits proliferation and cytokine expression in human, mouse and rat lymphocytes, and these inhibitory effects have been associated with induction of cytotoxic T-lymphocyte antigen 4 mRNA and protein in the presence of TIRC7 antibodies. In vivo, anti-TIRC7 antibodies prevent kidney transplant rejection in rats and heart allograft rejection in mice. Treatment with an anti-TIRC7 antibody as monotherapy or in combination with TNFalpha blockade inhibits disease progression in collagen-induced arthritis. TIRC7 expression decreases in the peripheral blood of humans who have undergone cardiac transplant prior to clinical rejection, and is therefore a promising noninvasive tool for the prediction of rejection. Thus, targeting of TIRC7 may lead to the development of specific and effective therapeutic and diagnostic approaches by unifying relevant cellular and molecular responses in T- and B-cell subsets, and represents a promising new pathway for immune regulation in transplantation and autoimmune disease.
膜蛋白T细胞免疫反应cDNA 7（TIRC7）在抗原刺激后于淋巴细胞亚群中短暂表达。针对TIRC7细胞外结构域的抗体的作用证明了TIRC7在免疫激活中的重要性。体外靶向TIRC7可抑制人、小鼠和大鼠淋巴细胞的增殖及细胞因子表达，且这些抑制作用与在TIRC7抗体存在下细胞毒性T淋巴细胞抗原4 mRNA和蛋白的诱导有关。在体内，抗TIRC7抗体可预防大鼠的肾移植排斥反应及小鼠的心脏同种异体移植排斥反应。用抗TIRC7抗体作为单一疗法或与肿瘤坏死因子α阻断剂联合治疗可抑制胶原诱导性关节炎的疾病进展。在临床排斥反应发生前接受心脏移植的人的外周血中TIRC7表达降低，因此它是预测排斥反应的一种有前景的非侵入性工具。因此，靶向TIRC7可能通过统一T细胞和B细胞亚群中的相关细胞和分子反应，导致开发出特异性和有效的治疗及诊断方法，并且代表了移植和自身免疫性疾病免疫调节的一条有前景的新途径。
