Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes.
T cells are postulated to contribute to the injury of the oligodendrocyte-myelin complex underlying the demyelinating disease multiple sclerosis (MS). The apparent lack of class I or II major histocompatibility complex (MHC) expression in situ on human oligodendrocytes and the consistent failure to identify a universal myelin antigen in MS suggest that the immune damage might be mediated by effector T cells that are capable of reacting in an antigen-nonspecific and possibly MHC-unrestricted manner, such as T cells expressing the gamma-delta T-cell receptor. Since gamma-delta T cells are reported to be present in MS plaques and an increased number are found in the cerebrospinal fluid of patients with MS, we directly examined whether gamma-delta T cells are capable of inducing injury to human oligodendrocytes. We found, using a 6-hour 51Cr release assay, that oligodendrocytes cultured from surgically resected human brain specimens were effectively lysed in a dose-dependent manner by human gamma-delta T cells (28 +/- 5% mean specific lysis, n = 6, at an effector-target ratio of 20:1). Although heat shock protein HSP72, a putative gamma-delta T-cell recognition molecule, could be induced in vitro in our oligodendrocytes, an antibody to HSP72 did not inhibit gamma-delta T cell-mediated lysis of oligodendrocytes. These results suggest that gamma-delta T cells gaining entry into the central nervous system may be deleterious to oligodendrocytes and thus may contribute to the pathogenesis of MS.
Freedman
M S
MS
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Ruijs
T C
TC
Selin
L K
LK
Antel
J P
JP
D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D004827:Epilepsy / Q000473:pathology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D009836:Oligodendroglia / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D006360:Heat-Shock Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta