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CD4+and CD8+CD28(nu...
CD4+and CD8+CD28(null) T Cells Are Cytotoxic to Autologous Muscle Cells in Patients With Polymyositis
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Pandya, Jayesh M. (författare)
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Venalis, Paulius (författare)
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- Al-Khalili, Lubna (författare)
- KTH
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Hossain, Mohammad Shahadat (författare)
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Stache, Vanessa (författare)
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- Lundberg, Ingrid E. (författare)
- Karolinska Institutet
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- Malmström, Vivianne (författare)
- Karolinska Institutet
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Fasth, Andreas E. R. (författare)
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(creator_code:org_t)
- 2016-07-27
- 2016
- Engelska.
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 68:8, s. 2016-2026
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Objective. 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. Methods. 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. Results. 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-gamma (IFN gamma) in coculture than did CD28+ T cells. The myotoxic effects of CD28(null) T cells were reduced upon the blocking of perforin, cytokines, and HLA. Addition of IFN gamma or tumor necrosis factor did not induce skeletal muscle cell death in the absence of T cells; however, it did up-regulate HLA expression on muscle cells. Conclusion. Myotoxicity of CD4+ and CD8+ CD28(null) T cells is mediated by directed perforin-dependent killing and can be further influenced by IFN gamma-induced HLA expression on muscle cells. The data suggest that CD28(null) T cells are key effector cells that contribute to the muscle cell damage in polymyositis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Experimental Autoimmune Myositis
- Monoclonal-Antibody Analysis
- Acute Coronary Syndromes
- Inclusion-Body Myositis
- Rheumatoid-Arthritis
- Inflammatory Myopathies
- Mononuclear-Cells
- Immunosuppressive Treatment
- Costimulatory Molecules
- Pathogenic Features
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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