免疫学
移植
抗原
效应器
肾
免疫记忆
生物
医学
免疫系统
免疫
内科学
遗传学
作者
Khodor I. Abou‐Daya,Roger Tieu,Daqiang Zhao,Rayan Rammal,Faruk Sacirbegovic,Amanda Williams,Warren D. Shlomchik,Martin H. Oberbarnscheidt,Fadi G. Lakkis
出处
期刊:Science immunology
[American Association for the Advancement of Science]
日期:2021-03-04
卷期号:6 (57)
被引量:87
标识
DOI:10.1126/sciimmunol.abc8122
摘要
Tissue-resident memory T cells (TRM) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into TRM and subsequently caused allograft rejection. TRM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and retransplantation experiments. Graft TRM proliferated locally, produced interferon-γ upon restimulation, and their in vivo depletion attenuated rejection. The vast majority of antigen-specific and polyclonal TRM lacked phenotypic and transcriptional exhaustion markers. Single-cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue-resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft TRM that maintain rejection locally. Targeting these TRM could improve renal transplant outcomes.
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