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Römer, C; Engel, O; Winek, K; Hochmeister, S; Zhang, T; Royl, G; Klehmet, J; Dirnagl, U; Meisel, C; Meisel, A.
Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome after experimental stroke.
J Neurosci. 2015; 35(20):7777-7794 Doi: 10.1523/JNEUROSCI.1532-14.2015 [OPEN ACCESS]
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Hochmeister Sonja

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Stroke-induced immunodepression (SIDS) is an essential cause of poststroke infections. Pharmacological inhibition of SIDS appears promising in preventing life-threatening infections in stroke patients. However, SIDS might represent an adaptive mechanism preventing autoreactive immune responses after stroke. To address this, we used myelin oligodendrocyte glycoprotein (MOG) T-cell receptor transgenic (2D2) mice where >80% of peripheral CD4(+) T cells express a functional receptor for MOG. We investigated in a murine model of middle cerebral artery occlusion the effect of blocking SIDS by inhibiting body's main stress axes, the sympathetic nervous system (SNS) with propranolol and the hypothalamic-pituitary-adrenal axis (HPA) with mifepristone. Blockade of both stress axes robustly reduced infarct volumes, decreased infection rate, and increased long-term survival of 2D2 and C57BL/6J wild-type mice. Despite these protective effects, blockade of SIDS increased CNS antigen-specific Type1 T helper cell (Th1) responses in the brains of 2D2 mice 14 d after middle cerebral artery occlusion. One month after experimental stroke, 2D2 mice developed signs of polyradiculitis, which were diminished by SIDS blockade. Adoptive transfer of CD4(+) T cells, isolated from 2D2 mice, into lymphocyte-deficient Rag-1KO mice did not reveal differences between SIDS blockade and vehicle treatment in functional long-term outcome after stroke. In conclusion, inhibiting SIDS by pharmacological blockade of body's stress axes increases autoreactive CNS antigen-specific T-cell responses in the brain but does not worsen functional long-term outcome after experimental stroke, even in a mouse model where CNS antigen-specific autoreactive T-cell responses are boosted. Copyright © 2015 the authors 0270-6474/15/357777-18$15.00/0.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Autoimmunity -
CD4-Positive T-Lymphocytes - immunology
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - physiopathology
Female -
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Infarction, Middle Cerebral Artery - immunology
Infarction, Middle Cerebral Artery - physiopathology
Mice -
Mice, Inbred C57BL -
Myelin-Oligodendrocyte Glycoprotein - metabolism
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - metabolism
Th1 Cells - immunology
Th1 Cells - metabolism

Find related publications in this database (Keywords)
CNS autoreactivity
murine stroke
stroke-induced immunodeficiency syndrome
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