Brain, Vol. 123, No. 8, 1660-1666,
August 2000
© 2000 Oxford University Press
Expression of the co-stimulatory molecule BB-1, the ligands CTLA-4 and CD28 and their mRNAs in chronic inflammatory demyelinating polyneuropathy
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Correspondence to:
Marinos C. Dalakas, MD, Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 4N248, 10 Center DR MSC 1382, Bethesda, MD 20892-1382, USA E-mail: dalakasm{at}ninds.nih.gov
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.
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