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  • Title: Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies.
    Author: Murata K, Dalakas MC.
    Journal: Am J Pathol; 1999 Aug; 155(2):453-60. PubMed ID: 10433938.
    Abstract:
    To examine if the muscle fibers in patients with inflammatory myopathies have the potential to behave as antigen presenting cells (APCs), we investigated the expression of costimulatory molecules BB-1, B7-1 (CD80), and B7-2 (CD86), and their counterreceptors, CD28 or CTLA-4 (CD152), in the muscle biopsies of patients with polymyositis (PM), PM associated with human immunodeficiency virus infection (HIV-PM), sporadic inclusion body myositis (s-IBM), dermatomyositis (DM), and normal or disease controls. The expression of the B7 family of molecules on the muscle fibers was limited to BB-1. In PM, HIV-PM, and s-IBM, but not the disease controls, the nonnecrotic, MHC-class I-expressing muscle fibers, invaded or not by CD8+ T cells, had prominent membrane expression of BB-1. Several of the BB-1-positive fibers bound strongly in a cell-to-cell contact with their CD28 or CTLA-4 ligands on the autoinvasive CD8+ T cells, as confirmed by confocal microscopy. By reverse transcription-polymerase chain reaction, the expression of CD28 and CTLA-4 was up-regulated in PM, HIV-PM, and s-IBM, but not the controls. Because the BB-1-positive fibers expressed MHC-class I antigen and bound to up-regulated counterreceptors CD28 and CTLA-4 on the autoinvasive CD8+ T cells only in PM, HIV-PM, and s-IBM, the BB-1 molecule in these diseases should have a functional role in antigen presentation and T cell differentiation. These findings complement recent studies and suggest that in PM, HIV-PM, and s-IBM the muscle fibers are not only targets of CD8+ cytotoxic T cells but may also behave as "professional" APC.
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