Expanded T cell receptor Vβ–restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28null T cells
Open Access
- 29 October 2010
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 62 (11), 3457-3466
- https://doi.org/10.1002/art.27665
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 CD28null 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 CD28null T cells. The T cell receptor (TCR) Vβ 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+CD28null and CD4+CD28null T cells, which represented the TCR Vβ–expanded T cells in sporadic IBM. Such CD28null T cells were abundant both in the inflamed muscle tissue and in the circulation. Although the specific TCR Vβ expansions varied between patients, both CD8+CD28null and CD4+CD28null T cells consistently displayed a highly proinflammatory and cytotoxic potential. Conclusion 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+CD28null T cells may exert cytotoxic effects directly on muscle fibers due to a cytotoxic potential similar to that in CD8+ T cells.This publication has 46 references indexed in Scilit:
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