Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies

Am J Pathol. 1999 Aug;155(2):453-60. doi: 10.1016/s0002-9440(10)65141-3.


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.

MeSH terms

  • AIDS-Related Opportunistic Infections / metabolism
  • AIDS-Related Opportunistic Infections / pathology
  • Abatacept
  • Antigens, CD
  • Antigens, Differentiation / metabolism*
  • Antigens, Differentiation, B-Lymphocyte / analysis
  • B7-1 Antigen / analysis
  • B7-1 Antigen / metabolism*
  • CD28 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class II / analysis
  • Humans
  • Immunoconjugates*
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Muscles / anatomy & histology
  • Muscles / metabolism
  • Muscular Dystrophies / metabolism
  • Myositis, Inclusion Body / metabolism*
  • Polymyositis / metabolism*
  • RNA, Messenger / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, B-Lymphocyte
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunoconjugates
  • RNA, Messenger
  • invariant chain
  • Abatacept