In silico investigation of novel biological pathways: The role of CD200 in regulation of T cell priming in experimental autoimmune encephalomyelitis

Biosystems ◽  
2013 ◽  
Vol 112 (2) ◽  
pp. 107-121 ◽  
Author(s):  
Richard B. Greaves ◽  
Mark Read ◽  
Jon Timmis ◽  
Paul S. Andrews ◽  
James A. Butler ◽  
...  
Keyword(s):  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
In Silico ◽  
Biological Pathways ◽  
Autoimmune Encephalomyelitis ◽  
T Cell Priming ◽  
Experimental Autoimmune

scholarly journals The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE

2015 ◽  
Vol 37 (1) ◽  
pp. 269-275 ◽  
Author(s):  
Ramona Halmer ◽  
Laura Davies ◽  
Yang Liu ◽  
Klaus Fassbender ◽  
Silke Walter
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Autoimmune Encephalomyelitis ◽  
Immune Receptors ◽  
Experimental Autoimmune

Background: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. Methods: In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. Results: In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. Conclusion: The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis.

Noradrenaline modulates CD4+ T cell priming in rat experimental autoimmune encephalomyelitis: a role for the α1-adrenoceptor

2019 ◽  
Vol 67 (2-3) ◽  
pp. 223-240 ◽  
Author(s):  
Ivan Pilipović ◽  
Ivana Vujnović ◽  
Zorica Stojić-Vukanić ◽  
Raisa Petrović ◽  
Duško Kosec ◽  
...  
Keyword(s):  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cd4 T Cell ◽  
Autoimmune Encephalomyelitis ◽  
T Cell Priming ◽  
Experimental Autoimmune

scholarly journals Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis.

1995 ◽  
Vol 182 (1) ◽  
pp. 75-85 ◽  
Author(s):  
B L McRae ◽  
C L Vanderlugt ◽  
M C Dal Canto ◽  
S D Miller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Tissue Damage ◽  
Acute Disease ◽  
Epitope Spreading ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Experimental Autoimmune

The role of epitope spreading in the pathology of relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) was examined. Using peripherally induced immunologic tolerance as a probe to analyze the neuropathologic T cell repertoire, we show that the majority of the immunopathologic reactivity during the acute phase of R-EAE in SJL/J mice induced by active immunization with the intact proteolipid (PLP) molecule is directed at the PLP139-151 epitope and that responses to secondary encephalitogenic PLP epitopes may contribute to the later relapsing phases of disease. Intermolecular epitope spreading was demonstrated by showing the development of T cell responses to PLP139-151 after acute disease in mice in which R-EAE was initiated by the transfer of T cells specific for the non-cross-reactive MBP84-104 determinant. Intramolecular epitope spreading was demonstrated by showing that endogenous host T cells specific for a secondary encephalitogenic PLP epitope (PLP178-191) are demonstrable by both splenic T cell proliferative and in vivo delayed-type hypersensitivity responses in mice in which acute central nervous system damage was initiated by T cells reactive with the immunodominant, non-cross-reactive PLP139-151 sequence. The PLP178-191-specific responses are activated as a result of and correlate with the degree of acute tissue damage, since they do not develop in mice tolerized to the initiating epitope before expression of acute disease. Most importantly, we show that the PLP178-191-specific responses are capable of mediating R-EAE upon adoptive secondary transfer to naive recipient mice. Furthermore, induction of tolerance to intact PLP (which inhibits responses to both the initiating PLP139-151 epitope and to the PLP178-191 epitope) after the acute disease episode is sufficient to prevent relapsing disease. These results strongly support a contributory role of T cell responses to epitopes released as a result of acute tissue damage to the immunopathogenesis of relapsing clinical episodes and have important implications for the design of antigen-specific immunotherapies for the treatment of chronic autoimmune disorders in humans.

scholarly journals The Effect of Aqueous Extract of Tarragon on Clinical Symptoms and T Cell Differentiation in Experimental Autoimmune Encephalomyelitis

2019 ◽  
Author(s):  
Tayebeh Nowras ◽  
Mohammad Fereidouni ◽  
Hamidreza Safari ◽  
Mohsen Naseri
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Aqueous Extract ◽  
T Cell Differentiation ◽  
Autoimmune Encephalomyelitis ◽  
Therapeutic Benefits ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is one of the autoimmune diseases that affects the central nervous system (CNS) and causes myelin loss and axonal damage. Recent studies have shown the important role of autoreactive T cells in the pathogenesis of MS. One of the plants in the Astersa family, which has therapeutic benefits, is Artemisia dracunculus L. or Tarragon. In this study, the role of aqueous extract of Tarragon in suppressing Th1 and Th17 cell differentiation and ameliorating experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in C57BL/6 female mice by Hook kit MOG35-55/CFA Emulsion PTX and one group was treated with Tarragon at a dose of 500 mg/kg. Mice were euthanized on day 33 post-immunization, spleens were removed for assessing Th1, Th17 and Treg cells by flow cytometry. We provided evidence that Tarragon (500 mg/kg) significantly ameliorated clinical scores of EAE. We did not observe significant alterations in T cell differentiation to Th1, Th17 or Treg in the spleen of mice during EAE. This is the first experimental evidence showing that administration of aqueous extract of Tarragon reduces the severity of EAE, but the protective effect of Tarragon is independent of alteration in T cells in the spleen. These results suggest other mechanisms for the effectiveness of this extract in improving the EAE process.

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