Expression of the co-stimulatory molecule BB-1, the ligands CTLA-4 and CD28 and their mRNAs in chronic inflammatory demyelinating polyneuropathy.
To examine whether the Schwann cells in patients with autoimmune neuropathies have the potential to behave as professional antigen-presenting cells, we investigated the expression of the co-stimulatory molecules BB-1, B7-1 (CD80) B7-2 (CD86) and their counter-receptors CD28 or CTLA-4 (CD152) at the protein and mRNA levels in sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP associated with human immunodeficiency virus infection (HIV-CIDP), IgM paraproteinaemic neuropathy and normal or non-immune axonal neuropathy. In single- and double-labelling experiments, we used the S-100 antigen as a pan-Schwann cell marker, myelin-associated glycoprotein as a marker for myelinating Schwann cells and the fibrillary acidic protein as a marker for unmyelinating Schwann cells. The expression of the B7 family of molecules was limited to BB-1 and was observed only on the Schwann cells. There was constitutive expression of BB-1 on unmyelinating Schwann cells in all nerves studied. However, in CIDP and HIV-CIDP, but not the other diseases, there was prominent upregulation of BB-1 on the myelinating Schwann cells. The endoneurial T cells in the proximity of BB-1-positive Schwann cells expressed the CD28 or CTLA-4 counter-receptors. Reverse transcription-polymerase chain reaction confirmed that these ligands were upregulated only in CIDP. Because the myelinating BB-1-positive Schwann cells expressed HLA-DR antigen, the findings indicate that, in CIDP, Schwann cells possess the necessary markers to function as antigen-presenting cells.
Murata
K
K
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
Dalakas
M C
MC
D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D060908:CTLA-4 Antigen; D005260:Female; D006801:Humans; D018796:Immunoconjugates; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008024:Ligands; D012333:RNA, Messenger; D000069594:Abatacept