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J Invest Dermatol. 2017 May;137(5):1042-1050. doi: 10.1016/j.jid.2016.11.037. Epub 2016 Dec 22.

Skin-Resident Effector Memory CD8+CD28- T Cells Exhibit a Profibrotic Phenotype in Patients with Systemic Sclerosis.

Author information

1
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
2
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
3
Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
4
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
5
Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Electronic address: paf23@pitt.edu.

Abstract

Loss of CD28 expression by CD8+ T cells occurs with age and during chronic inflammatory conditions. CD8+CD28- T cells are a heterogeneous cell subpopulation whose function ranges from immunosuppressive to effector. Here we analyzed the role of CD8+CD28- T cells in the pathogenesis of systemic sclerosis (SSc), a connective tissue disorder characterized by autoimmunity, vasculopathy, and extensive cutaneous and visceral fibrosis. We show that the frequency of CD8+CD28- T cells is increased in the blood and affected skin of SSc patients, independent of patient age, and correlates with the extent of skin fibrosis. We found that most skin-tropic CD8+CD28- T cells are resident in the skin lesions of patients in the early stage of the disease, exhibit an effector memory phenotype, and present a strong cytolytic activity ex vivo. Skin-resident and circulating SSc CD8+CD28- T cells produce high levels of the profibrotic cytokine IL-13, which induces collagen production by normal and SSc dermal fibroblasts. Thus, our findings indicate that CD8+CD28- T cells represent a pathogenic T-cell subset in SSc and likely play a critical role in the early stage of SSc skin disease.

Comment in

PMID:
28012718
PMCID:
PMC5433864
DOI:
10.1016/j.jid.2016.11.037
[Indexed for MEDLINE]
Free PMC Article

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