T cell exhaustion is associated with antigen abundance and promotes transplant acceptance.,American Journal of Transplantation

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T cell exhaustion is associated with antigen abundance and promotes transplant acceptance.
American Journal of Transplantation ( IF 8.9 ) Pub Date : 2020-03-17 , DOI: 10.1111/ajt.15870
Dawei Zou _{1,

2} , Yulin Dai ₃ , Xiaolong Zhang ₁ , Guohua Wang ₁ , Xiang Xiao ₁ , Peilin Jia ₃ , Xian C Li _{1,

4} , Zhiyong Guo ₂ , Wenhao Chen _{1,

4}

Affiliation

Exhaustion of T cells limits their ability to clear chronic infections or eradicate tumors. Here, in the context of transplant, we investigated whether T cell exhaustion occurs and has a role in determining transplant outcome. A peptide/MHC tetramer‐based approach was used to track exhausted CD8⁺ T cells in a male‐to‐female skin transplant model. Transplant of large whole‐tail skins, but not small tail skins (0.8 cm × 0.8 cm), led to exhaustion of anti‐male tetramer⁺ CD8⁺ T cells and subsequently the acceptance of skin grafts. To study CD4⁺ T cell exhaustion, we used the TCR‐transgenic B6 TEa cells that recognize a major transplant antigen I‐Eα from Balb/c mice. TEa cells were adoptively transferred either into B6 recipients that received Balb/c donor skins or into CB6F1 mice that contained an excessive amount of I‐Eα antigen. Adoptively transferred TEa cells in skin‐graft recipients were not exhausted. By contrast, virtually all adoptively transferred TEa cells were exhausted in CB6F1 mice. Those exhausted TEa cells lost ability to reject Balb/c skins upon further transfer into lymphopenic B6.Rag1^−/− mice. Hence, T cell exhaustion develops in the presence of abundant antigen and promotes transplant acceptance. These findings are essential for better understanding the nature of transplant tolerance.

中文翻译：

T 细胞耗竭与抗原丰度相关并促进移植接受。

T 细胞的耗尽限制了它们清除慢性感染或根除肿瘤的能力。在这里，在移植的背景下，我们研究了 T 细胞衰竭是否发生以及是否在确定移植结果中起作用。基于肽/MHC 四聚体的方法用于追踪男性到女性皮肤移植模型中耗尽的 CD8 ⁺ T 细胞。移植大的全尾皮，而不是小尾皮（0.8 cm × 0.8 cm），导致抗雄性四聚体⁺ CD8 ⁺ T 细胞耗尽，随后接受皮肤移植。研究 CD4 ⁺T 细胞耗竭时，我们使用了 TCR 转基因 B6 TEa 细胞，这些细胞识别来自 Balb/c 小鼠的主要移植抗原 I-Eα。TEa 细胞被过继转移到接受 Balb/c 供体皮肤的 B6 受体或含有过量 I-Eα 抗原的 CB6F1 小鼠中。皮肤移植受体中过继转移的 TEa 细胞并未耗尽。相比之下，几乎所有过继转移的 TEa 细胞在 CB6F1 小鼠中都已耗尽。那些耗尽的 TEa 细胞在进一步转移到淋巴细胞减少的 B6 中后失去了排斥 Balb/c 皮肤的能力。Rag1 ^-/-小鼠。因此，T 细胞衰竭在存在丰富抗原的情况下发展并促进移植接受。这些发现对于更好地了解移植耐受性的本质至关重要。

更新日期：2020-03-17

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