耶鲁大学医学院Joseph Craft小组的一项最新研究发现了系统性自身免疫中的器官损伤是由来自组织引流淋巴结的干细胞样CD8⁺ T细胞介导的。相关论文于2026年4月20日发表在《免疫学》杂志上。

该课题组人员研究了CD8⁺ T细胞浸润红斑狼疮易感小鼠肾脏的起源、分化和功能后果。肾引流淋巴结中的TCF-1+干细胞样CD8⁺ T细胞经历T细胞受体（TCR）依赖、抗原驱动的扩增，分化为细胞毒性肾浸润细胞，在CD4⁺ T细胞帮助和白细胞介素(IL)-21和IL-15信号的作用下促进组织损伤。CD8⁺ T细胞分化的标志是持续的AP-1活性和细胞毒性功能，尽管免疫检查点的表达增加。狼疮性肾炎患者肾脏中CD8⁺ T细胞分化的平行程序反映了共同的发病机制。在红斑狼疮中发现了一种类似慢性感染和癌症的T细胞分化程序；然而，CD8⁺ T细胞在系统性自身免疫中，尽管有终末分化，但仍保留了效应功能。

研究人员表示，虽然B细胞耐受性丧失、自身抗体产生和免疫复合物沉积是系统性红斑狼疮（SLE）的标志，但肾脏CD8⁺ T细胞浸润是狼疮肾炎预后不良的最佳预测指标，狼疮肾炎是SLE的一种严重表现。

附：英文原文

Title: Organ injury in systemic autoimmunity is mediated by stem-like CD8+ T cells arising from tissue-draining lymph nodes

Author: Jafar Al Souz, Yulong Wei, Can Cui, Rihao Qu, Jin-Young Choi, Fang Wang, Steven J. Moioffer, Julia Barrett, Irene Chernova, Manvitha Nadella, Emily R. Siniscalco, Gilbert Moeckel, Nikhil S. Joshi, Ping-Min Chen, Arnon Arazi, Jennifer Anolik, William Apruzzese, Arnon Arazi, Jennifer Barnas, Michael Belmont, Celine Berthier, Michael B. Brenner, Jill Buyon, Phillip Carlucci, Robert Clancy, Sean Connery, Maria Dall’Era, Anne Davidson, Wade DeJager, Kristina Deonaraine, Betty Diamond, Patrick J. Dunn, Thomas Eisenhaure, Andrea Fava, Jennifer Goff, Beatrice Goilav, Jennifer Grossman, Joel Guthridge, Nir Hacohen, David Hildeman, Jeffery Hodgin, Paul Hoover, Raymond Hsu, Kazuyoshi Ishigaki, Mariko Ishimori, Peter Izmirly, Judith James, Tony Jones, Ken Kalunian, Diane L. Kamen, Ilya Korsunsky, Matthias Kretzler, Manjunath Kustagi, James Lederer, Jessica Li, David Lieb, Susan Macwana, Holden Maecker, Rong Mao, Maureen McMahon, Joseph Mears, Raji Menon, Nghia Millard, Pavel Morozov, Aparna Nathan, Fernanda Payan-Schober, Michael Peters, Michelle Petri, Chaim Putterman, Deepak A. Rao, Soumya Raychaudhuri, Bill Robinson, Saori Sakaue, Hemant Suryawanshi, Thomas Tuschl, P.J. Utz, Kathryn Weinand, Michael Weisman, David Wofsy, Steve Woodle, Qian Xiao, Fan Zhang, Ya-Chi Ho, Joseph Craft

Issue&Volume: 2026-04-20

Abstract: Although loss of B cell tolerance, autoantibody production, and immune complex deposition are hallmarks of systemic lupus erythematosus (SLE), CD8+ T cell infiltration in the kidneys is the best predictor of poor prognosis in lupus nephritis, a severe manifestation of SLE. Here, we examined the origin, differentiation, and functional consequences of CD8+ T cells infiltrating kidneys in lupus-prone mice. TCF-1+ stem-like CD8+ T cells in renal-draining lymph nodes underwent T cell receptor (TCR)-dependent, antigen-driven expansion with differentiation into cytotoxic kidney-infiltrating cells that promoted tissue injury contingent on CD4+ T cell help and interleukin (IL)-21 and IL-15 signaling. CD8+ T cell differentiation was marked by persistent AP-1 activity and cytotoxic function despite increased expression of immune checkpoints. A parallel program of CD8+ T cell differentiation in the kidneys of patients with lupus nephritis reflected shared pathogenesis. Thus, a T cell differentiation program analogous to that in chronic infections and cancer is found in lupus; however, CD8+ T cells in systemic autoimmunity retain effector function despite terminal differentiation.

DOI: 10.1016/j.immuni.2026.03.022

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00133-0