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CD8+CD28- t cells are cytotoxic and pro-fibrotic in patients with scleroderma

CD8+CD28- T cells are cytotoxic and pro-fibrotic in patients...

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第十届全国免疫学学术大会

作者： GANG LI Alissa L Moss thomas A Medsger Jr robyn t domsic Mary R Lucas Dana E Ivanco Robert Lafyatis Donna B Stolz Patrizia Fuschiotti Children's Hospital of Soochow University Department of Immunology University of Pittsburgh School of Medicine Department of Medicine Division of Rheumatology and Clinical Immunology University of Pittsburgh School of Medicine Rheumatology Section Boston University School of Medicine Department of Cell Biology University of Pittsburgh School of Medicine

Objective:Loss of CD28 expression by CD8+t cells occurs with age and during chronic inflammatory ***8+CD28-t cells are a heterogeneous cell subpopulation ranging from immunosuppressive to effector *** showed previously that Interleukin(IL)-13-producing CD8+t cells are implicated in the pathogenesis of systemic sclerosis(SSc).Here we analyzed the role of CD8+CD28-t cells in SSc pathogenesis in an age-and disease-controlled cohort of ***:Flow cytometry was employed to determine cell surface phenotype,cytokine production and cytotoxicity function of peripheral blood CD8+CD28-t cells from patients and *** and apoptosis properties of CD8+t-cell subsets were measured by CFSE and Annexin V *** and immunohistochemistry were used to assess expression of cytokine and markers of cytotoxicity by CD8+t cells in the affected skin of ***:We found that the proportion of CD8+CD28-t cells is increased in patients with SSc independently of patient age and correlates with the extent of skin *** CD8+CD28-t cells are found in the effector and effector/memory subsets,secrete IL-13,and are ***,they exhibit normal levels of proliferation and susceptibility to ***,IL-13-producing CD8+t cells that express markers of cytotoxicity are found in the sclerotic skin of ***:We provide new insight into the pathogenesis of SSc by identifying a pathogenic CD8+t-cell subset characterized by profibrotic IL-13 overproduction and direct cellular *** novel molecular targets may open avenues for future therapeutic intervention.

关键词： scleroderm CD8+CD28-t cells perforin granzyme B IL-13

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