scholarly journals Impaired Development of CD4+ CD25+ Regulatory T Cells in the Absence of STAT1

2003 ◽  
Vol 199 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Takeaki Nishibori ◽  
Yoshinari Tanabe ◽  
Leon Su ◽  
Michael David
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Regulatory T Cells ◽  
Cell Receptor ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Self Tolerance ◽  
Opposing Effects ◽  
Experimental Autoimmune

Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use the signal transducer and activator of transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1-deficient mice expressing a transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this autoimmune disease appears to be triggered by a reduced number as well as a functional impairment of the CD4+ CD25+ regulatory T cells in STAT1-deficient animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient hosts is sufficient to prevent the development of autoimmune disease. These results demonstrate an essential role of STAT1 in the maintenance of immunological self-tolerance.

scholarly journals Essential Role of CD8+CD122+ Regulatory T Cells in the Recovery from Experimental Autoimmune Encephalomyelitis

2008 ◽  
Vol 180 (2) ◽  
pp. 825-832 ◽  
Author(s):  
Young-Ho Lee ◽  
Yoshiyuki Ishida ◽  
Muhaimin Rifa’i ◽  
Zhe Shi ◽  
Ken-ichi Isobe ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Essential Role ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Genetically modified hematopoietic stem/progenitor cells that produce IL-10–secreting regulatory T cells

2019 ◽  
Vol 116 (7) ◽  
pp. 2634-2639 ◽  
Author(s):  
Sze-Ling Ng ◽  
Ester Leno-Duran ◽  
Dibyendu Samanta ◽  
Steven C. Almo ◽  
Jack L. Strominger
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Tnf Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Hematopoietic Stem ◽  
High Level ◽  
Level Production ◽  
Experimental Autoimmune

Random amino acid copolymers used in the treatment of multiple sclerosis in man or experimental autoimmune encephalomyelitis (EAE) in mice [poly(Y,E,A,K)n, known as Copaxone, and poly(Y,F,A,K)n] function at least in part by generation of IL-10–secreting regulatory T cells that mediate bystander immunosuppression. The mechanism through which these copolymers induce Tregs is unknown. To investigate this question, four previously described Vα3.2 Vβ14 T cell receptor (TCR) cDNAs, the dominant clonotype generated in splenocytes after immunization of SJL mice, that differed only in their CDR3 sequences were utilized to generate retrogenic mice. The high-level production of IL-10 as well as IL-5 and small amounts of the related cytokines IL-4 and IL-13 by CD4+ T cells isolated from the splenocytes of these mice strongly suggests that the TCR itself encodes information for specific cytokine secretion. The proliferation and production of IL-10 by these Tregs was costimulated by activation of glucocorticoid-induced TNF receptor (GITR) (expressed at high levels by these cells) through its ligand GITRL. A mechanism for generation of cells with this specificity is proposed. Moreover, retrogenic mice expressing these Tregs were protected from induction of EAE by the appropriate autoantigen.

scholarly journals Studies in B7-Deficient Mice Reveal a Critical Role for B7 Costimulation in Both Induction and Effector Phases of Experimental Autoimmune Encephalomyelitis

1999 ◽  
Vol 190 (5) ◽  
pp. 733-740 ◽  
Author(s):  
Tammy T. Chang ◽  
Claudia Jabs ◽  
Raymond A. Sobel ◽  
Vijay K. Kuchroo ◽  
Arlene H. Sharpe
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Wild Type ◽  
Autoimmune Encephalomyelitis ◽  
Autoreactive T Cells ◽  
Effector Phase ◽  
Deficient Mice ◽  
Experimental Autoimmune

The importance of B7 costimulation in regulating T cell expansion and peripheral tolerance suggests that it may also play a significant regulatory role in the development of autoimmune disease. It is unclear whether B7 costimulation is involved only in the expansion of autoreactive T cells in the periphery, or if it is also required for effector activation of autoreactive T cells in the target organ for mediating tissue injury and propagating autoimmune disease. In this study, the role of B7–CD28 costimulation and the relative importance of B7 costimulators for the induction and effector phases of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide were examined. Wild-type, B7-1/B7-2–deficient mice, or CD28-deficient C57BL/6 mice were immunized with MOG 35-55 peptide. Mice lacking both B7-1 and B7-2 or CD28 showed no or minimal clinical signs of EAE and markedly reduced inflammatory infiltrates in the brain and spinal cord. However, mice lacking either B7-1 or B7-2 alone developed clinical and pathologic EAE that was comparable to EAE in wild-type mice, indicating overlapping functions for B7-1 and B7-2. Resistance to EAE was not due to a lack of induction of T helper type 1 (Th1) cytokines, since T cells from B7-1/B7-2−/− mice show reduced proliferative responses, but greater interferon γ production compared with T cells from wild-type mice. To study the role of B7 molecules in the effector phase of the disease, MOG 35-55–specific T lines were adoptively transferred into the B7-1/B7-2−/− and wild-type mice. Clinical and histologic EAE were markedly reduced in B7-1/B7-2−/− compared with wild-type recipient mice. These results demonstrate that B7 costimulation has critical roles not only in the initial activation and expansion of MOG-reactive T cells, but also in the effector phase of encephalitogenic T cell activation within the central nervous system.

PS1-011. The Role Of Type I Interferon Signaling Via T Cells In The Early Phase Of Experimental Autoimmune Encephalomyelitis (EAE)

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 18-19
Author(s):  
Nadia Kavrochorianou ◽  
Maria Evangelidou ◽  
Michael Tovey ◽  
George Thyphronitis ◽  
Sylva Haralambous
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Early Phase ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Chloroquine Treatment Enhances Regulatory T Cells and Reduces the Severity of Experimental Autoimmune Encephalomyelitis

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65913 ◽  
Author(s):  
Rodolfo Thomé ◽  
Adriel S. Moraes ◽  
André Luis Bombeiro ◽  
Alessandro dos Santos Farias ◽  
Carolina Francelin ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Chloroquine Treatment ◽  
Experimental Autoimmune

scholarly journals Mgat5 Deficiency in T Cells and Experimental Autoimmune Encephalomyelitis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ani Grigorian ◽  
Michael Demetriou
Keyword(s):  
T Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Cell Receptor ◽  
Protein Glycosylation ◽  
Autoimmune Encephalomyelitis ◽  
Glycosylation Pathway ◽  
Experimental Autoimmune ◽  
Surface Glycoproteins

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease initiated by autoreactive T cells. Mgat5, a gene in the Asn (N-) linked protein glycosylation pathway, associates with MS severity and negatively regulates experimental autoimmune encephalomyelitis (EAE) and spontaneous inflammatory demyelination in mice. N-glycan branching by Mgat5 regulates interaction of surface glycoproteins with galectins, forming a molecular lattice that differentially controls the concentration of surface glycoproteins. T-cell receptor signaling, T-cell proliferation, TH1 differentiation, and CTLA-4 endocytosis are inhibited by Mgat5 branching. Non-T cells also contribute to MS pathogenesis and express abundant Mgat5 branched N-glycans. Here we explore whether Mgat5 deficiency in myelin-reactive T cells is sufficient to promote demyelinating disease. Adoptive transfer of myelin-reactive Mgat5−/− T cells into Mgat5+/+ versus Mgat5−/− recipients revealed more severe EAE in the latter, suggesting that Mgat5 branching deficiency in recipient naive T cells and/or non-T cells contribute to disease pathogenesis.

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