Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies.
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.
Murata
K
K
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Dalakas
M C
MC
D017088:AIDS-Related Opportunistic Infections / Q000378:metabolism / Q000473:pathology; D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D060908:CTLA-4 Antigen; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018796:Immunoconjugates; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000033:anatomy & histology / Q000378:metabolism; D009136:Muscular Dystrophies / Q000378:metabolism; D018979:Myositis, Inclusion Body / Q000378:metabolism*; D017285:Polymyositis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018796:Immunoconjugates; D012333:RNA, Messenger; C045084:invariant chain; D000069594:Abatacept