Cd154 on the surface of CD4+CD25+ regulatory T cells contributes to skin transplant tolerance
Cd154 on the surface of CD4+CD25+ regulatory T cells contributes to skin transplant tolerance
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DOI：
10.1097/01.tp.0000093462.16309.73
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发表时间：
2003-11-15
期刊：
影响因子：
6.2
通讯作者：
Noelle, RJ
中科院分区：
文献类型：
--
作者：
Jarvinen, LZ;Blazar, BR;Noelle, RJ
背景已知将来自供体的全血（供体特异性输血）输注到受体中结合抗CD 154治疗可以延长同种异体移植物存活。人们普遍认为，抗CD 154治疗的有效性是由同种异体反应性CD 4（+）和CD 8（+）效应T细胞的失活引起的。最近的文献表明CD 4（+）CD 25（+）调节性T细胞参与了自身免疫和移植排斥的抑制，因此我们研究了CD 154阻断是否有效，因为它阻断了炎性T细胞的活化，或者直接影响了调节性T细胞。RAG（-/-）小鼠单独或联合供体特异性输血和抗CD 154过继输注CD 4（+）T细胞或群体亚群（CD 4（+）CD 25（+）或CD 4（+）CD 25（-）T细胞），并给予同种异体皮肤移植。移植的寿命随着时间的推移而确定。采用CD 154（-/-）CD 4（+）T细胞评价CD 154在移植物排斥和接受中的作用。CD 4（+）CD 25（+）调节性T细胞上的CD 154阻断（或CD 154缺失）增强了它们的免疫抑制活性，并且是体内抗CD 154诱导的免疫抑制的促成因素。在同种异体移植耐受模型中，如果CD 4（+）CD 25（+）调节性T细胞表达CD 154缺陷，则抗原和抗CD 154或抗原单独诱导抑制。在抗原暴露时中和调节性T细胞上的CD 154的功能诱导了抑制活性水平的提高，并且可能是抗CD 154治疗的长期治疗效果的促成因素。
Background. It is known that the infusion of whole blood from donors (donor-specific transfusion) into recipients combined with anti-CD154 therapy can prolong allograft; survival. It has generally been agreed that the effectiveness of anti-CD154 therapy is caused by the inactivation of alloreactive CD4(+) and CD8(+) effector T cells. The recent literature has implicated CD4(+)CD25(+) regulatory T cells in the suppression of autoimmunity and graft rejection, and we therefore examined whether CD154 blockade is effective because of its blockade of inflammatory T-cell activation or because of a direct impact on the regulatory T cells.Methods. RAG(-/-) mice were adoptively transfused with CD4(+) T cells or a subset of the population (CD4(+)CD25(+) or CD4(+)CD25(-) T cells) alone or in combination with donor-specific transfusion and anti-CD154 and given an allo-skin transplant. The longevity of the transplant was determined over time. CD154(-/-)CD4(+) T cells were used to assess the importance of CD154 in graft rejection and acceptance.Results. CD154 blockade (or loss of CD154) on CD4(+)CD25(+) regulatory T cells enhanced their immunosuppressive activities and was a contributing factor to anti-CD154-induced immune suppression in vivo. In a model of allograft tolerance, suppression was elicited by antigen and anti-CD154 or antigen alone if the CD4(+)CD25(+) regulatory T cells were deficient in CD154 expression.Conclusions. Neutralizing the function of CD154 on regulatory T cells upon antigen exposure induces heightened levels of suppressive activities and is likely a contributing factor to the long-lived therapeutic effects of anti-CD154 treatment.