Stem-like CD4 + T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis

Author:

Sato Yuki123ORCID,Jain Abhinav3ORCID,Ohtsuki Shozo123ORCID,Okuyama Hirohisa3ORCID,Sturmlechner Ines3ORCID,Takashima Yoshinori123ORCID,Le Kevin-Phu C.123ORCID,Bois Melanie C.4,Berry Gerald J.5ORCID,Warrington Kenneth J.1,Goronzy Jörg J.136ORCID,Weyand Cornelia M.1236ORCID

Affiliation:

1. Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.

2. Department of Cardiovascular Disease, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.

3. Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.

4. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA.

5. Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.

6. Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA.

Abstract

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4 + T cell population with stem cell–like features. CD4 + T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription factor T cell factor 1 (TCF1), had high proliferative potential, and gave rise to two effector populations, Eomesodermin (EOMES) + cytotoxic T cells and B cell lymphoma 6 (BCL6) + T follicular helper-like cells. TCF1 hi CD4 + T cells expressing the interleukin 7 receptor (IL-7R) sustained vasculitis in serial transplantation experiments. Thus, TCF1 hi CD4 + T cells function as disease stem cells and promote chronicity and autonomy of autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like CD4 + T cells instead of only effector T cells.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Artérite à cellules géantes;La Revue de Médecine Interne;2023-12

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