Immune Reconstitution Following Rabbit Antithymocyte Globulin
Immune Reconstitution Following Rabbit Antithymocyte Globulin
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DOI：
10.1111/j.1600-6143.2010.03210.x
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发表时间：
2010-09-01
影响因子：
8.8
通讯作者：
Murphy, B.
中科院分区：
文献类型：
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作者：
Gurkan, S.;Luan, Y.;Murphy, B.
耗竭诱导疗法通常用于预防急性排斥反应和改善移植结果。消耗剂对t细胞亚群和随后的t细胞重构的影响尚不完全明确。我们用流式细胞术检测了兔抗胸腺细胞球蛋白（rATG）对儿童和成人肾移植受者外周血t细胞库的影响。我们发现，虽然大鼠g有效地减少了CD45RA+CD27+幼稚和CD45RO+CD27+中枢记忆CD4+ T细胞，但对CD45RO+CD27- CD4+效应记忆或CD45RA+CD31-、CD45RO+CD27+和CD45RO+CD27- CD8+ T细胞亚群的影响很小。当我们对CD31+近期胸腺移植物和CD45RA+/RO+ T细胞进行动力学分析时，我们发现了胸腺生成和稳态增殖有助于免疫重建的证据。我们还研究了大鼠组对外周血CD4+Foxp3+ T细胞的影响。我们发现，在成人中，给药大鼠诱导具有Treg表型的T细胞外周扩增和新的胸腺迁移，而CD4+Foxp3+胸腺来源的T细胞在儿童中占主导地位，提供了第一个证据，证明大鼠在体内诱导Treg。总的来说，我们的数据表明，rATG改变了移植后对记忆效应T细胞的调节平衡，为其如何积极影响移植结果提供了解释。
Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T-cell subsets and subsequent T-cell reconstitution are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T-cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naive and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27- CD4+ effector memory or CD45RA+CD31-, CD45RO+CD27+ and CD45RO+CD27- CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG-induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome.