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.

DOI: 10.4049/jimmunol.0803688

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@article{Fasth2009TCI, title={T cell infiltrates in the muscles of patients with dermatomyositis and polymyositis are dominated by CD28null T cells.}, author={Andreas E. R. Fasth and Maryam Dastmalchi and Afsar Rahbar and Stina Salomonsson and Jayesh M. Pandya and Eva Lindroos and Inger Nennesmo and Karl-Johan Malmberg and Cecilia S{\"{o}derberg-Naucl{\'e}r and Christina Trollmo and Ingrid E. Lundberg and Vivianne Malmstr{\"{o}m}, journal={Journal of immunology}, year={2009}, volume={183 7}, pages={4792-9} }