Delineation of tissue damage mechanisms in experimental autoimmune encephalomyelitis (EAE). I. Cell detachment and lysis induced by encephalitogenic CD4+ T lymphocytes.
Myelin basic protein (MBP) reactive CD4+ T lymphocytes, capable of inducing experimental autoimmune encephalomyelitis (EAE), were examined for their ability to damage target cells of central nervous system (CNS) origin. Damage was assessed by monitoring detachment of adherent astrocytes from substratum and astrocyte lysis. MBP-specific, but non-encephalitogenic CD4+ T cells mediated astrocyte detachment but not lysis. However, encephalitogenic CD4+ T cell lines were more efficient in causing astrocyte detachment and could also cause astrocyte lysis. The detachment and lytic activities of the MBP-reactive T cell lines tested were often independent of the presence of specific antigen, and were not restricted to syngeneic major histocompatibility (MHC) antigens. MBP often augmented the detaching and, if lytic, lytic activities of these T cells. The encephalitogenic CD4+ T cells also detached and lysed allogeneic 'bystander' fibroblasts in the presence of unlabelled syngeneic astrocytes, suggesting the involvement of a soluble mediator(s). Although MBP is essential for the initiation of EAE, the presence of MBP on cells of CNS origin, such as astrocytes and oligodendrocytes, does not appear to be necessary for their damage by MBP-specific CD4+ T cells. Immune CD4+ T cells, which penetrate the CNS, may disorganize brain tissue structure by lysing astrocytes directly and by damaging other brain cells indirectly by soluble mediators. Thus cellular detachment, in addition to cell lysis, mediated by MBP-specific CD4+ cells may contribute to EAE pathogenesis.
Halachmi
E
E
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Ben-Nun
A
A
Lehmann
D
D
Karussis
D
D
Wekerle
H
H
Berke
G
G
D000818:Animals; D001253:Astrocytes / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000473:pathology*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein; D009417:Nerve Tissue / Q000473:pathology*; D009836:Oligodendroglia / Q000473:pathology
D004676:Myelin Basic Protein