Long term immunologic consequences of experimental stroke and mucosal tolerance
J. Michael Gee,Dannielle Zierath,Jessica Hadwin,Anna V. Savos,Angela Kalil,Matthew Thullbery,Kyra J. Becker +6 more
TLDR
Induction of immunological tolerance to MBP is associated with improved outcome after stroke, however, this study raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.Abstract:
An inflammatory insult following middle cerebral artery occlusion (MCAO) is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP). Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional outcome early after stroke. In this study, we sought to determine the long term immunologic consequences of experimental stroke and induction of mucosal tolerance. Male Lewis rats were tolerized to MBP or ovalbumin (OVA) by intranasal administration prior to MCAO and administration of lipopolysaccharide (LPS). Neurological outcome was assessed at set points after MCAO and animals sacrificed at 3 months; the immune response to MBP in brain and spleen was determined using ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by immunocytochemistry. Animals that developed a pro-inflammatory (TH 1) response to MBP experienced worse outcome, while those that developed a regulatory response (TREG) experienced better outcome. A TREG response in spleen was also associated with decreased inflammation and an increase in the number of FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO was associated with a tendency to develop a TH 1 response to MBP by 3 months after MCAO. These data show that induction of immunological tolerance to MBP is associated with improved outcome after stroke. This study, however, raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.read more
Citations
More filters
Journal ArticleDOI
Regulatory T Cell in Stroke: A New Paradigm for Immune Regulation
TL;DR: Evidence of FoxP3+CD25+CD4+ Tregs as potentially important immunomodulators in stroke pathogenesis is summarized and further investigations for possible immunotherapeutic strategies by modulating the quantity and/or functional effects of FoxTregs in stroke patients are highlighted.
Journal ArticleDOI
Regulatory T cell is critical for interleukin-33-mediated neuroprotection against stroke.
Xinjing Liu,Ruiyao Hu,Lulu Pei,Pan Si,Chunhui Wang,Xuan Tian,Xiao Wang,Han Liu,Beng Wang,Zongping Xia,Yuming Xu,Bo Song +11 more
TL;DR: Overall, the findings showed that IL-33 afforded neuroprotection against ischemic brain injury by enhancing ST2-dependent regulatory T-cell expansion and activation via a mechanism involving anti-apoptosis proteins and cytokines, representing a promising immune modulatory target for the treatment of stroke.
Journal ArticleDOI
Autoimmune responses to brain following stroke.
TL;DR: It is proposed that the microenvironment within the lymph nodes and brain is altered by systemic inflammation and allows for bystander activation of lymphocytes and the development of autoimmune responses to brain antigens following cerebral ischemic injury.
Journal ArticleDOI
A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke.
Hsu Tung Lee,Shih Ping Liu,Chen Huan Lin,Sophie Wei Lee,Chung Y. Hsu,Huey-Kang Sytwu,Chia Hung Hsieh,Woei Cherng Shyu +7 more
TL;DR: Findings indicate that passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.
Journal ArticleDOI
Adaptive Immunity Regulation and Cerebral Ischemia
Xingping Qin,Xingping Qin,Farhana Akter,Lingxia Qin,Jing Cheng,Mei Guo,Shun Yao,Shun Yao,Zhihong Jian,Renzhong Liu,Songlin Wu +10 more
TL;DR: This review highlights the key components of the adaptive immune system that are activated following cerebral ischemia that are equally important in preventing autoimmunity of the body to brain antigens that are released into the peripheral system as a result of BBB compromise.
References
More filters
Journal ArticleDOI
Reversible middle cerebral artery occlusion without craniectomy in rats.
TL;DR: Seven of eight rats that underwent permanent occlusion of the MCA had resolving moderately severe neurologic deficits and unilateral infarcts averaging 37.6 +/- 5.5% of the coronal sectional area at 72 hours after the onset of Occlusion.
Journal ArticleDOI
Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.
Joshua B. Bederson,Lawrence H. Pitts,Miles Tsuji,Merry C. Nishimura,Richard L. Davis,Henry M. Bartkowski +5 more
TL;DR: In this article, the authors examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia.
Journal ArticleDOI
Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.
Konstantin Prass,Christian Meisel,Conny Höflich,Johann S. Braun,E. Halle,Tilo Wolf,Karsten Ruscher,Ilya V. Victorov,Josef Priller,Ulrich Dirnagl,Hans-Dieter Volk,Andreas Meisel +11 more
TL;DR: It is suggested that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
Journal ArticleDOI
Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells
TL;DR: It is demonstrated that T cells that are specific for different myelin epitopes generate populations characterized by different T helper type 17 (TH17) to T helpertype 1 (TH1) ratios depending on the functional avidity of interactions between TCR and peptide-MHC complexes.
Journal ArticleDOI
Experimental Stroke Induces Massive, Rapid Activation of the Peripheral Immune System:
Halina Offner,Sandhya Subramanian,Susan M. Parker,Michael Afentoulis,Arthur A. Vandenbark,Arthur A. Vandenbark,Patricia D. Hurn +6 more
TL;DR: Data show for the first time that focal cerebral ischemia results in dynamic and widespread activation of inflammatory cytokines, chemokines, and CCR in the peripheral immune system.