Human muscle cells express the costimulatory molecule B7-H3, which modulates muscle-immune interactions.
OBJECTIVE
Interactions between the family of B7 ligands and their receptors are increasingly recognized as crucial for stimulation and/or inhibition of immune responses. The present study was undertaken to examine the expression and functional relevance of B7 homolog 3 (B7-H3), a novel B7 homolog attributed significant immunoregulatory functions, in human muscle cells in vivo and in vitro.


METHODS
Thirty-five muscle biopsy specimens obtained from patients with polymyositis, dermatomyositis, inclusion body myositis, or noninflammatory myopathies and normal controls were analyzed by immunohistochemistry for B7-H3 expression. The expression of B7-H3 protein on primary human myoblasts and TE671 muscle rhabdomyosarcoma cells was studied by flow cytometry and Western blot analysis. B7-H3 small interfering RNA (siRNA) was used to study the impact of knockdown of B7-H3 on CD8+ cell-mediated lysis in skeletal muscle cells.


RESULTS
B7-H3 was not detectable on normal muscle fibers. In contrast, its expression was markedly increased on muscle fibers from patients with inflammatory myopathies. Cell-surface staining was most prominent in the contact areas between muscle fibers and inflammatory cells. B7-H3 protein was detected on myoblasts cultured from control and myositis patient muscle tissue as well as in TE671 muscle rhabdomyosarcoma cells. Knockdown of B7-H3 by siRNA in TE671 cells enhanced CD8+ T cell-specific lysis, indicating a functional role of B7-H3 in the protection of skeletal muscle from immune-mediated lysis.


CONCLUSIONS
Our results demonstrate that human muscle cells express B7-H3, a functional coinhibitory molecule of the B7 family. B7-H3 may play an important role in muscle-immune interactions, providing further evidence of the active role of muscle cells in local immunoregulatory processes.
Waschbisch
Anne
A
University of Wuerzburg, Wuerzburg, Germany, and University of Erlangen, Erlangen, Germany.
Wintterle
Sabine
S
Lochmüller
Hanns
H
Walter
Maggie C
MC
Wischhusen
Jörg
J
Kieseier
Bernd C
BC
Wiendl
Heinz
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D060887:B7 Antigens; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D003882:Dermatomyositis / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000737:chemistry / Q000276:immunology*; D019042:Muscle Neoplasms / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism; D018979:Myositis, Inclusion Body / Q000378:metabolism; D017285:Polymyositis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology*; D012208:Rhabdomyosarcoma / Q000378:metabolism
D015703:Antigens, CD; D060887:B7 Antigens; C423237:CD276 protein, human; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic