CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome

Jennifer Y Barr; Xiaofang Wang; David K Meyerholz; Scott M Lieberman

doi:10.1038/icb.2017.38

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CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome

Journal article

Peer reviewed

CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome

Jennifer Y Barr, Xiaofang Wang, David K Meyerholz and Scott M Lieberman

Immunology and cell biology, Vol.95(8), pp.684-694

09/2017

DOI: 10.1038/icb.2017.38

PMCID: PMC5595634

PMID: 28465508

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Abstract

Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity. Within the lacrimal and salivary glands of NOD mice, CD8 T cells were proliferating, expressed an activated phenotype, and produced inflammatory cytokines. Transfer of purified CD8 T cells isolated from the cervical lymph nodes (LNs) of NOD mice into NOD-severe combined immunodeficiency recipients resulted in inflammation of the lacrimal glands, but was not sufficient to cause inflammation of the salivary glands. Lacrimal gland-infiltrating CD8 T cells displayed a cytotoxic phenotype, and epithelial cell damage in the lacrimal glands was observed in recipients of CD8 T cells regardless of the presence of CD4 T cells. Collectively, our results demonstrate that CD8 T cells have a pathogenic role in lacrimal gland autoimmunity. The gland-specific pathogenicity of CD8 T cells makes them a valuable resource to further understand the mechanisms that discriminate lacrimal versus salivary gland autoimmunity and for the development of new therapeutics that target the early stages of disease.

Autoimmunity

Salivary Glands - immunology

Cell Proliferation

Cytokines - metabolism

CD8-Positive T-Lymphocytes - transplantation

Lymphocyte Activation

Humans

Mice, Inbred C57BL

Cells, Cultured

Sjogren's Syndrome - immunology

Male

Adoptive Transfer

Mice, SCID

Animals

Epithelial Cells - immunology

Inflammation Mediators - metabolism

Female

Mice, Inbred NOD

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

Lacrimal Apparatus - pathology

Cytotoxicity, Immunologic

Disease Models, Animal

Details

Title: Subtitle: CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome
Creators: Jennifer Y Barr - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Xiaofang Wang - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
David K Meyerholz - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Scott M Lieberman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Immunology and cell biology, Vol.95(8), pp.684-694
DOI: 10.1038/icb.2017.38
PMID: 28465508
PMCID: PMC5595634
NLM abbreviation: Immunol Cell Biol
ISSN: 0818-9641
eISSN: 1440-1711
Grant note: S10 OD016199 / NIH HHS K08 EY022344 / NEI NIH HHS
Language: English
Date published: 09/2017
Academic Unit: Stead Family Department of Pediatrics; Pathology; Rheumatology, Allergy, and Immunology
Record Identifier: 9984083884702771

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