scholarly journals Identification of T cell epitopes on human proteolipid protein and induction of experimental autoimmune encephalomyelitis in HLA class II-transgenic mice

2004 ◽  
Vol 34 (1) ◽  
pp. 280-290 ◽  
Author(s):  
Ashutosh K. Mangalam ◽  
Meenakshi Khare ◽  
Christopher Krco ◽  
Moses Rodriguez ◽  
Chella David
Keyword(s):  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Transgenic Mice ◽  
Proteolipid Protein ◽  
Class Ii ◽  
Hla Class Ii ◽  
T Cell Epitopes ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Priming of Myelin-Specific T Cells in the Absence of Dendritic Cells Results in Accelerated Development of Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Thaiphi Luu ◽  
Julie F. Cheung ◽  
Hanspeter Waldner
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Experimental Autoimmune

AbstractExperimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), is predominantly mediated by pro-inflammatory CD4+ T cell responses to CNS antigens, including myelin proteolipid protein (PLP). Dendritic cells (DCs) are considered critical for inducing T cell responses against infectious agents, but the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear.To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.

scholarly journals HLA Class II Polymorphisms Modulate Gut Microbiota and Experimental Autoimmune Encephalomyelitis Phenotype

2021 ◽  
Vol 5 (8) ◽  
pp. 627-646
Author(s):  
Shailesh K. Shahi ◽  
Soham Ali ◽  
Camille M. Jaime ◽  
Natalya V. Guseva ◽  
Ashutosh K. Mangalam
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Class Ii ◽  
Hla Class Ii ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Human Commensal Prevotella histicola Ameliorates Disease as Effectively as Interferon-Beta in the Experimental Autoimmune Encephalomyelitis

2020 ◽  
Vol 11 ◽  
Author(s):  
Shailesh K. Shahi ◽  
Samantha N. Jensen ◽  
Alexandra C. Murra ◽  
Na Tang ◽  
Hui Guo ◽  
...  
Keyword(s):  
T Cells ◽  
Environmental Factors ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Transgenic Mice ◽  
Environmental Factor ◽  
Interferon Beta ◽  
Hla Class Ii ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Gut microbiota has emerged as an important environmental factor in the pathobiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Both genetic and environmental factors have been shown to play an important role in MS. Among genetic factors, the human leukocyte antigen (HLA) class II allele such as HLA-DR2, DR3, DR4, DQ6, and DQ8 show the association with the MS. We have previously used transgenic mice expressing MS susceptible HLA class II allele such as HLA-DR2, DR3, DQ6, and DQ8 to validate significance of HLA alleles in MS. Although environmental factors contribute to 2/3 of MS risk, less is known about them. Gut microbiota is emerging as an imporatnt environmental factor in MS pathogenesis. We and others have shown that MS patients have distinct gut microbiota compared to healthy control (HC) with a lower abundance of Prevotella. Additionally, the abundance of Prevotella increased in patients receiving disease-modifying therapies (DMTs) such as Copaxone and/or Interferon-beta (IFNβ). We have previously identified a specific strain of Prevotella (Prevotella histicola), which can suppress experimental autoimmune encephalomyelitis (EAE) disease in HLA-DR3.DQ8 transgenic mice. Since Interferon-β-1b [IFNβ (Betaseron)] is a major DMTs used in MS patients, we hypothesized that treatment with the combination of P. histicola and IFNβ would have an additive effect on the disease suppression. We observed that treatment with P. histicola suppressed disease as effectively as IFNβ. Surprisingly, the combination of P. histicola and IFNβ was not more effective than either treatment alone. P. histicola alone or in combination with IFNβ increased the frequency and number of CD4+FoxP3+ regulatory T cells in the gut-associated lymphoid tissue (GALT). Treatment with P. histicola alone, IFNβ alone, and in the combination decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4+ T cells in the CNS. Additionally, P. histicola alone or IFNβ alone or the combination treatments decreased CNS pathology, characterized by reduced microglia and astrocytic activation. In conclusion, our study indicates that the human gut commensal P. histicola can suppress disease as effectively as commonly used MS drug IFNβ and may provide an alternative treatment option for MS patients.

scholarly journals Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250340
Author(s):  
Thaiphi Luu ◽  
Julie F. Cheung ◽  
Jennifer Baccon ◽  
Hanspeter Waldner
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is an established animal model of multiple sclerosis (MS). Inflammatory CD4+ T cell responses directed against CNS antigens, including myelin proteolipid protein (PLP), are key mediators of EAE. Dendritic cells (DCs) are critical for the induction of T cell responses against infectious agents. However, the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear. To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.

scholarly journals Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis

1999 ◽  
Vol 189 (6) ◽  
pp. 1005-1010 ◽  
Author(s):  
Daniel J. Cua ◽  
Herve Groux ◽  
David R. Hinton ◽  
Stephen A. Stohlman ◽  
Robert L. Coffman
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Transgenic Mice ◽  
Mhc Class Ii ◽  
Cell Function ◽  
Class Ii ◽  
Interleukin 10 ◽  
T Helper 1 ◽  
Autoimmune Encephalomyelitis ◽  
Autoreactive T Cell ◽  
Experimental Autoimmune

The effectiveness of interleukin 10 (IL-10) in the treatment of autoimmune-mediated central nervous system inflammation is controversial. Studies of the model system, experimental autoimmune encephalomyelitis (EAE), using various routes, regimens, and delivery methods of IL-10 suggest that these variables may affect its immunoregulatory function. To study the influence of these factors on IL-10 regulation of EAE pathogenesis, we have analyzed transgenic mice expressing human IL-10 (hIL-10) transgene under the control of a class II major histocompatibility complex (MHC) promoter. The hIL-10 transgenic mice are highly resistant to EAE induced by active immunization, and this resistance appears to be mediated by suppression of autoreactive T cell function. Myelin-reactive T helper 1 cells are induced but nonpathogenic in the IL-10 transgenic mice. Antibody depletion confirmed that EAE resistance is dependent on the presence of the transgenic IL-10. Mice expressing the hIL-10 transgene but not the endogenous murine IL-10 gene demonstrated that transgenic IL-10 from MHC class II–expressing cells is sufficient to block induction of EAE. This study demonstrates that IL-10 can prevent EAE completely if present at appropriate levels and times during disease induction.

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