title: Expanded T cell receptor Vβ-restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28null T cells.
abstract: OBJECTIVE
  Sporadic inclusion body myositis (IBM) is characterized by T cell infiltrates in muscle tissue, but their functional role is unclear. Systemic signs of inflammation are lacking, and the absence of beneficial effects following immunosuppression has challenged the notion of a role for the immune system. This study was undertaken to investigate the phenotype and functionality of T cells, specifically a subset of proinflammatory, cytotoxic, and apoptosis-resistant T cells defined as CD28(null) T cells, in the pathogenesis of sporadic IBM.
  
  
  METHODS
  A cohort of 27 patients with sporadic IBM was analyzed for the frequency of circulating and muscle-infiltrating CD28(null) T cells. The T cell receptor (TCR) V(β) usage was determined using flow cytometry and immunohistochemistry. Anti-CD3-stimulated peripheral blood mononuclear cells were analyzed for intracellular interferon-γ and cytotoxic potential by flow cytometry.
  
  
  RESULTS
  We found striking accumulations of both CD8+CD28(null) and CD4+CD28(null) T cells, which represented the TCR V(β) -expanded T cells in sporadic IBM. Such CD28(null) T cells were abundant both in the inflamed muscle tissue and in the circulation. Although the specific TCR V(β) expansions varied between patients, both CD8+CD28(null) and CD4+CD28(null) T cells consistently displayed a highly proinflammatory and cytotoxic potential.
  
  
  CONCLUSIONS
  Our results suggest that CD28null T cell expansions represent the previously described expanded T cell subsets in sporadic IBM, and their proinflammatory capacity and presence in both muscle tissue and the circulation may imply a role of immune activation in sporadic IBM. In addition, CD4+CD28(null) T cells may exert cytotoxic effects directly on muscle fibers due to a cytotoxic potential similar to that in CD8+ T cells.
authors.affiliation: Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden. Jayesh.Pandya@ki.se
authors.forename: Jayesh M
authors.initials: JM
authors.lastname: Pandya
authors.forename: Andreas E R
authors.initials: AE
authors.lastname: Fasth
authors.forename: Mei
authors.initials: M
authors.lastname: Zong
authors.forename: Snjolaug
authors.initials: S
authors.lastname: Arnardottir
authors.forename: Lara
authors.initials: L
authors.lastname: Dani
authors.forename: Eva
authors.initials: E
authors.lastname: Lindroos
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology*; D018979:Myositis, Inclusion Body / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell