Preferential priming of alloreactive T cells with indirect reactivity.
Preferential priming of alloreactive T cells with indirect reactivity.
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DOI：
10.1111/j.1600-6143.2009.02578.x
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Kang SM
中科院分区：
文献类型：
--
作者：
Brennan TV;Jaigirdar A;Hoang V;Hayden T;Liu FC;Zaid H;Chang CK;Bucy RP;Tang Q;Kang SM
直接和间接途径在同种免疫应答中的相对贡献尚未完全阐明。我们报告了一种新的小鼠TCR转基因系统，可以同时跟踪移植后的CD 4-直接（CD 4-d），CD 4-间接（CD 4-i）和CD 8-直接（CD 8-d）途径。使用该系统，我们已经观察到移植后相对于CD 4-d和CD 8-d T细胞，CD 4-i T细胞的增殖显著更大。此外，更大比例的CD 4-iT细胞获得效应子表型。我们还分析了内源性，野生型T细胞使用酶联免疫斑点分析。在幼稚小鼠中，未检测到具有间接反应性的T细胞，但具有直接反应性的T细胞丰富。然而，皮肤或异位心脏移植后10天，CD 4-i T细胞占CD 4+应答的约10%。与CD 4-i通路的增加的引发一致，我们观察到CD 4-i T细胞进一步富集在迁移到同种异体移植物的效应细胞和在排斥后持续存在的记忆样T细胞中。因此，CD 4-i通路的启动在移植后是有利的，允许罕见的群体迅速成为急性同种异体移植物排斥中CD 4 + T细胞应答的主要组分。这一观察结果是否可推广到其他模型仍有待确定。
The relative contributions of the direct and indirect pathways in alloimmune responses have not been fully elucidated. We report a novel murine TCR transgenic system that can simultaneously track the CD4-direct (CD4-d), CD4-indirect (CD4-i), and CD8-direct (CD8-d) pathways after transplantation. Using this system, we have observed a profoundly greater proliferation of CD4-i T cells relative to CD4-d and CD8-d T cells after transplantation. Furthermore, a much larger proportion of CD4-i T cells attain an effector phenotype. We also analyzed endogenous, wild-type T cells using enzyme-linked immunospot analysis. In naive mice, T cells with indirect reactivity were undetectable, but T cells with direct reactivity were abundant. However, 10 days after skin or heterotopic heart transplantation, CD4-i T cells comprised approximately 10% of the CD4+ response. Consistent with increased priming of the CD4-i pathway, we observed that the CD4-i T cells were further enriched in the effector cells migrating to the allograft and in the memory-like T cells persisting after rejection. Thus, priming of the CD4-i pathway is favored after transplantation, allowing a rare population to rapidly become a major component of the CD4+ T cell response in acute allograft rejection. The generalizability of this observation to other models remains to be determined.
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影响因子：
5.4
作者：
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DOI：
10.1084/jem.20042521
发表时间：
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期刊：
The Journal of experimental medicine
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