title: T cell infiltrates in the muscles of patients with dermatomyositis and polymyositis are dominated by CD28null T cells.
abstract: Dermatomyositis and polymyositis are disabling rheumatic diseases characterized by an appreciable number of T cells infiltrating muscle tissue. The precise phenotype, function and specificity of these cells remain elusive. In this study, we aimed to characterize T cells in muscle tissue and circulation and to investigate their association to clinical phenotype. Twenty-four patients with dermatomyositis and 42 with polymyositis were screened for frequency of CD4+CD28(null) and CD8+CD28(null) T cells in peripheral blood by flow cytometry. Presence of these cells in inflamed muscle tissue from 13 of these patients was analyzed by three-color immunofluorescence microscopy. Effector functions, proliferation and Ag specificity were analyzed by flow cytometry after in vitro stimulation. The clinical relevance of CD28(null) T cells was analyzed by multiple regression analyses including six separate and combined disease variables. We demonstrate that muscle-infiltrating T cells are predominantly CD4+CD28(null) and CD8+CD28(null) T cells in patients with dermatomyositis and polymyositis. Muscle-infiltrating CD28(null) T cells were found already at time of diagnosis. Disease activity correlated with the frequency of CD8+ T cells in the inflamed muscles of polymyositis patients. Circulating CD4+CD28(null) and CD8+CD28(null) T cells were significantly more frequent in human CMV (HCMV) seropositive individuals, responded to HCMV Ag stimulation, and correlated with disease duration. These cells also display a proinflammatory cytokine profile, contain perforin and lack the costimulatory molecule CD28. Our observations imply that CD28(null) T cells represent clinically important effector cells in dermatomyositis and polymyositis, and that HCMV might play a role in propagating disease in a subset of patients.
authors.affiliation: Rheumatology Unit, Center for Molecular Medicine L8:04, Karolinska University Hospital, Stockholm S-171 76, Sweden. andreas.fasth@ki.se
authors.forename: Andreas E R
authors.initials: AE
authors.lastname: Fasth
authors.forename: Maryam
authors.initials: M
authors.lastname: Dastmalchi
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.forename: Stina
authors.initials: S
authors.lastname: Salomonsson
authors.forename: Jayesh M
authors.initials: JM
authors.lastname: Pandya
authors.forename: Eva
authors.initials: E
authors.lastname: Lindroos
authors.forename: Inger
authors.initials: I
authors.lastname: Nennesmo
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Nauclér
authors.forename: Christina
authors.initials: C
authors.lastname: Trollmo
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
mesh_terms: D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D003882:Dermatomyositis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017285:Polymyositis / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D018106:CD28 Antigens