Expression of heat shock protein-65 by oligodendrocytes in vivo and in vitro: implications for multiple sclerosis.
We studied immunoreactivity for heat shock proteins (HSPs) in multiple sclerosis (MS) brain tissue and detected HSP-65 in chronic MS plaques at the edge of thinly myelinated (or remyelinated) areas. Serial-section immunocytochemistry and double staining revealed that HSP-65+ cells represented reactive, immature oligodendrocytes with strong reactivity for myelin basic protein and weak reactivity for galactocerebroside. Mature oligodendrocytes outside MS plaques did not stain for HSP-65. Control brain sections showed no HSP-65 reactivity. Oligodendrocytes expressed HSP-65 in mixed glial cell cultures. In this system in vitro, oligodendrocytes, but not astrocytes, showed constitutive expression of HSP-65. There was immunoreactivity for HSP-72 in astrocytes in MS and non-MS brains to a similar extent but no association between HSP-72 reactivity and MS plaques. Interestingly, HSP-65+ oligodendrocytes colocalized with T lymphocytes expressing the gamma delta T-cell receptor (TcR). Since HSP-65 has been implicated as a major antigen recognized by TcR gamma delta lymphocytes, our findings might represent a new immunologic interaction within MS plaques that leads to the destruction of immature oligodendrocytes involved in remyelination.
Selmaj
K
K
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Brosnan
C F
CF
Raine
C S
CS
D000326:Adrenoleukodystrophy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism*; D015493:Paraparesis, Tropical Spastic / Q000378:metabolism / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013344:Subacute Sclerosing Panencephalitis / Q000378:metabolism / Q000473:pathology
D006360:Heat-Shock Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta