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Lysis of rat brain microvascular endothelial cells mediated by resting but not activated MBP-specific CD4+ T cell
B Engelhardt1, H Görlach, W Risau
1Max-Planck-Institut für physiologische und klinische Forschung, W.G. Kerckhoff-Institut, Abteilung Molekulare Zellbiologie, Bad Nauheim, Germany.
Abstract:
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.
Insights
Resting myelin basic protein (MBP)-specific T cells, not activated ones, lyse rat brain endothelial cells. This suggests a unique role for resting T cells in experimental autoimmune encephalomyelitis pathogenesis.
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Myelin basic protein (MBP)-specific T cells possess encephalitogenic and cytotoxic potential.
- These T cells can lyse glia cells and blood-brain barrier endothelial cells presenting autoimmunogenic MBP peptide.
Purpose of the Study:
- To investigate the distinct mechanisms of T cell-mediated cytotoxicity against rat brain endothelium (RBE).
- To determine the role of T cell activation state in RBE lysis.
Main Methods:
- Comparison of cytotoxic activity of activated vs. resting MBP-specific T cells against RBE.
- Assessment of T cell lines with varying antigen specificities for RBE lysis.
Main Results:
- Cytotoxicity against RBE was mediated exclusively by resting MBP-specific T cells.
- Activated MBP-specific T cell blasts showed significantly reduced RBE lysis.
- T cells specific for other antigens did not lyse RBE.
Conclusions:
- The cytotoxic reaction against endothelial cells differs fundamentally from classical T cell-mediated cytotoxicity.
- Resting MBP-specific T cells may play a crucial role in the pathogenesis of experimental autoimmune encephalomyelitis.