Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection

被引：0

作者：

Sanders, Jes M. ^{[1
]}

Banbury, Barbara L. ^{[2
]}

Schumacher, Erika L. ^{[2
]}

He, Jie ^{[1
]}

Sambandam, Yuvaraj ^{[1
]}

Fields, Paul A. ^{[2
]}

Gallon, Lorenzo ^{[3
,4
]}

Mathew, James M. ^{[1
,4
,5
]}

Leventhal, Joseph R. ^{[1
,4
]}

机构：

[1] Northwestern Univ, Comprehens Transplant Ctr, Dept Surg,Feinberg Sch Med, Div Organ Transplantat, Chicago, IL 60611 USA

[2] Adapt Biotechnol, Seattle, WA USA

[3] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Nephrol, Chicago, IL 60611 USA

[4] Northwestern Univ, Feinberg Sch Med, Simpson Querrey Inst BioNanotechnol, Chicago, IL 60611 USA

[5] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA

来源：

FRONTIERS IN IMMUNOLOGY | 2025年 / 16卷

基金：

美国国家卫生研究院;

关键词：

kidney transplant rejection; alloreactivity; T-cell receptor sequencing; T-cell mediated rejection; mechanisms of rejection; SUBCLINICAL REJECTION; ALLOGRAFTS; RECIPIENTS; SURVIVAL; HISTORY; NAIVE;

D O I：

10.3389/fimmu.2025.1516772

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Introduction Responses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elucidate signatures of kidney allograft rejection.Methods DRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4+ and CD8+ DRTC were flow-sorted, and the TCR sequences were identified using Adaptive Immunosequencing. DRTC were then tracked in post-transplant biopsies, blood, and urine samples in a cohort of kidney transplant recipients.Results In patients with an abnormal biopsy, the majority of CD8+ DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8+ DRTC were more abundant pre- and post-transplant in patients that received non-lymphodepletional induction and developed an abnormal biopsy when compared to stable patients. Additionally, DRTC were detected as early as two weeks post-transplant in the urine of some patients, with some of these clones subsequently identified in follow-up kidney biopsy samples.Discussion The findings of our study add to our understanding of T-cell alloreactivity following kidney transplantation and provide evidence for the role of pre-defined alloreactive T-cells in the development of allograft rejection.

引用

页数：13

共 39 条

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