T cell infiltrates in the muscles of patients with dermatomyositis and polymyositis are dominated by CD28null T cells.
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.
Fasth
Andreas E R
AE
Rheumatology Unit, Center for Molecular Medicine L8:04, Karolinska University Hospital, Stockholm S-171 76, Sweden. andreas.fasth@ki.se
Dastmalchi
Maryam
M
Rahbar
Afsar
A
Salomonsson
Stina
S
Pandya
Jayesh M
JM
Lindroos
Eva
E
Nennesmo
Inger
I
Malmberg
Karl-Johan
KJ
Söderberg-Nauclér
Cecilia
C
Trollmo
Christina
C
Lundberg
Ingrid E
IE
Malmström
Vivianne
V
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
D018106:CD28 Antigens