NK cells restrain cytotoxic CD8 + T cells in the submandibular gland via PD-1–PD-L1

IF 17.6 1区 医学 Q1 IMMUNOLOGY
Samantha M. Borys, Shanelle P. Reilly, Ian Magill, David Zemmour, Laurent Brossay
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引用次数: 0

Abstract

The increasing use of anti–programmed cell death 1 (PD-1) immune checkpoint blockade has led to the emergence of immune-related adverse events (irAEs), including dysfunction of the submandibular gland (SMG). In this study, we investigated the immunoregulatory mechanism contributing to the susceptibility of the SMG to irAEs. We found that the SMGs of PD-1–deficient mice and anti–programmed cell death ligand 1 (PD-L1)–treated mice harbor an expanded population of CD8 + T cells. We demonstrate that natural killer (NK) cells expressing PD-L1 tightly regulate CD8 + T cells in the SMG. When this immunoregulation is disrupted, CD8 + T cells clonally expand and acquire a unique transcriptional profile consistent with T cell receptor (TCR) activation. These clonally expanded cells phenotypically overlapped with cytotoxic GzmK + CD8 + T autoimmune cells identified in patients with primary Sjögren’s syndrome. Understanding how NK cells modulate CD8 + T cell activity in the SMG opens new avenues for preventing irAEs in patients undergoing checkpoint blockade therapies.
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来源期刊
Science Immunology
Science Immunology Immunology and Microbiology-Immunology
CiteScore
32.90
自引率
2.00%
发文量
183
期刊介绍: Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.
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