T cell exhaustion is associated with antigen abundance and promotes transplant acceptance.
T cell exhaustion is associated with antigen abundance and promotes transplant acceptance.
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DOI：
10.1111/ajt.15870
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Zou D;Dai Y;Zhang X;Wang G;Xiao X;Jia P;Li XC;Guo Z;Chen W
T 细胞的耗竭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 细胞耗竭是否发生以及在决定移植结果中的作用。基于肽/MHC 四聚体的方法用于追踪男性至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。为了研究 CD4+ T 细胞耗竭，我们使用了 TCR 转基因 B6 TEa 细胞，该细胞识别来自 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 受体中或转移到含有过量 I-Eα 抗原的 CB6F1 小鼠中。皮肤移植受者中过继转移的 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 小鼠中都被耗尽。这些耗尽的 TEa 细胞在进一步转移到淋巴细胞减少的 B6.Rag1−/− 小鼠中后失去了排斥 Balb/c 皮肤的能力。因此，在存在丰富抗原的情况下会出现 T 细胞耗竭，并促进移植接受。这些发现对于更好地了解移植耐受的本质至关重要。
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.
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DOI：
10.1073/pnas.1910298116
发表时间：
2019-11-19
影响因子：
11.1
作者：
Miller, Michelle L.;McIntosh, Christine M.;Alegre, Maria-Luisa
通讯作者：
Alegre, Maria-Luisa
影响因子：
12.3
作者：
Robinson MD;Oshlack A
通讯作者：
Oshlack A
DOI：
10.1126/science.aad0501
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tirosh I;Izar B;Prakadan SM;Wadsworth MH 2nd;Treacy D;Trombetta JJ;Rotem A;Rodman C;Lian C;Murphy G;Fallahi-Sichani M;Dutton-Regester K;Lin JR;Cohen O;Shah P;Lu D;Genshaft AS;Hughes TK;Ziegler CG;Kazer SW;Gaillard A;Kolb KE;Villani AC;Johannessen CM;Andreev AY;Van Allen EM;Bertagnolli M;Sorger PK;Sullivan RJ;Flaherty KT;Frederick DT;Jané-Valbuena J;Yoon CH;Rozenblatt-Rosen O;Shalek AK;Regev A;Garraway LA
通讯作者：
Garraway LA
影响因子：
8.8
作者：
Zhang, Hedong;Wu, Jie;Chen, Wenhao
通讯作者：
Chen, Wenhao
影响因子：
64.8
作者：
Khan, Omar;Giles, Josephine R.;Wherry, E. John
通讯作者：
Wherry, E. John