Skin-Resident Effector Memory CD8CD28 T Cells Exhibit a Profibrotic Phenotype in Patients with Systemic Sclerosis

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2016 Dec 26

PMID 28012718

Citations 35

Authors

Gang Li

Adriana T Larregina

Robyn T Domsic

Donna B Stolz

Thomas A Medsger Jr

Robert Lafyatis

Patrizia Fuschiotti

Affiliations

Soon will be listed here.

Abstract

Loss of CD28 expression by CD8 T cells occurs with age and during chronic inflammatory conditions. CD8CD28 T cells are a heterogeneous cell subpopulation whose function ranges from immunosuppressive to effector. Here we analyzed the role of CD8CD28 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 CD8CD28 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 CD8CD28 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 CD8CD28 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 CD8CD28 T cells represent a pathogenic T-cell subset in SSc and likely play a critical role in the early stage of SSc skin disease.

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