CD4+ and CD8+ CD28(null) T Cells Are Cytotoxic to Autologous Muscle Cells in Patients With Polymyositis

Arthritis & Rheumatology
Jayesh M PandyaAndreas E R Fasth

Abstract

Inflammatory T cell infiltrates in the skeletal muscle tissue of patients with polymyositis are dominated by CD28-negative effector (CD28(null) ) T cells of both the CD4 and CD8 lineage. These cells are potentially cytotoxic, and the aim of the present study was to develop a fully autologous cell culture system in which to investigate the functional contribution of such CD28(null) T cells to myotoxicity. In vitro cocultures of autologous skeletal muscle cells and T cell subsets obtained from 5 polymyositis patients were performed. Myotoxicity of T cells was quantified by calcein release and flow cytometric analyses. T cell degranulation was blocked with concanamycin A. Specific blocking of perforin, cytokines, and HLA was performed using antibodies. Both CD4+CD28(null) and CD8+CD28(null) T cells induced more muscle cell death than did their CD28+ counterparts. Differentiated muscle cells (myotubes) were more sensitive to T cell-mediated cell death than were their precursors (myoblasts). Both CD8+ and CD4+ CD28(null) T cells displayed perforin polarization toward muscle cells and secreted higher levels of granzyme B and interferon-γ (IFNγ) in coculture than did CD28+ T cells. The myotoxic effects of CD28(null) T cells were reduc...Continue Reading

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Citations

Jun 18, 2016·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Felicitas EscherHeinz-Peter Schultheiss
Jun 19, 2016·Mechanisms of Ageing and Development·Cecilia Söderberg-NauclérAfsar Rahbar
Feb 17, 2017·Current Opinion in Rheumatology·Ingrid E Lundberg, Jiri Vencovsky
Apr 21, 2018·Nature Reviews. Rheumatology·Frederick W MillerKanneboyina Nagaraju
Jun 20, 2018·Expert Review of Clinical Immunology·Dae Hyun YooChang-Hee Suh
Jan 28, 2021·European Journal of Immunology·Veronika NiederlovaOndrej Stepanek

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