Lysis of rat brain microvascular endothelial cells mediated by resting but not activated MBP-specific CD4+ T cell lines.
Previous work from this laboratory showed that the encephalitogenic potential of myelin basic protein (MBP)-specific T cells is inseparably associated with their cytotoxic potential. MBP-specific T cells lyse all cells that present autoimmunogenic MBP peptide in context of appropriate MHC class II determinants. Beside class II-induced glia cells, blood-brain barrier-derived endothelial cells were identified as highly susceptible target cells for cytotoxic MBP-specific T cells. Here we show that the cytotoxic reaction against endothelial cells essentially differs from cytotoxicity against other target cells. In contrast to classical T cell-mediated lytic responses, which are most efficiently executed by activated T cells, rat brain endothelium (RBE) lysis could only be mediated by resting T cells. Activated MBP-specific T cell blasts were not able to mediate strong RBE lysis. Furthermore, T cell lines with specificities for protein antigens other than MBP did not cause RBE lysis. A role of the cytolytic capacity of resting MBP-specific T cells in the pathogenesis of experimental autoimmune encephalomyelitis is probable.
Engelhardt
B
B
Max-Planck-Institut für physiologische und klinische Forschung, W.G. Kerckhoff-Institut, Abteilung Molekulare Zellbiologie, Bad Nauheim, Germany.
Görlach
H
H
Risau
W
W
Wekerle
H
H
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein