The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform
Benedikt Fritzsching - One of the best experts on this subject based on the ideXlab platform.
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Regulatory T cells in Experimental Autoimmune Disease
Springer Seminars in Immunopathology, 2006Co-Authors: Elisabeth Suri-payer, Benedikt FritzschingAbstract:During the past 10 years, CD4^+CD25^+Foxp3^+ regulatory T cells (Treg) have been extensively studied for their function in Autoimmune Disease. This review summarizes the evidence for a role of Treg in suppression of innate and adaptive immune responses in Experimental models of autoimmunity including arthritis, colitis, diabetes, Autoimmune encephalomyelitis, lupus, gastritis, oophoritis, prostatitis, and thyroiditis. Antigen-specific activation of Treg, but antigen-independent suppressive function, emerges as a common paradigm derived from several Disease models. Treg suppress conventional T cells (Tcon) by direct cell contact in vitro. However, downmodulation of dendritic cell function and secretion of inhibitory cytokines such as IL-10 and TGF-β might underlie Treg function in vivo. The final outcome of autoimmunity vs tolerance depends on the balance between stimulatory signals (Toll-like receptor engagement, costimulation, and antigen dose) and inhibitory signals from Treg. Whereas most Experimental settings analyze the capacity of Treg to prevent onset of Autoimmune Disease, more recent efforts indicate successful treatment of ongoing Disease. Thus, Treg are on the verge of moving from Experimental animal models into clinical applications in humans.
Elisabeth Suri-payer - One of the best experts on this subject based on the ideXlab platform.
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Regulatory T cells in Experimental Autoimmune Disease
Springer Seminars in Immunopathology, 2006Co-Authors: Elisabeth Suri-payer, Benedikt FritzschingAbstract:During the past 10 years, CD4^+CD25^+Foxp3^+ regulatory T cells (Treg) have been extensively studied for their function in Autoimmune Disease. This review summarizes the evidence for a role of Treg in suppression of innate and adaptive immune responses in Experimental models of autoimmunity including arthritis, colitis, diabetes, Autoimmune encephalomyelitis, lupus, gastritis, oophoritis, prostatitis, and thyroiditis. Antigen-specific activation of Treg, but antigen-independent suppressive function, emerges as a common paradigm derived from several Disease models. Treg suppress conventional T cells (Tcon) by direct cell contact in vitro. However, downmodulation of dendritic cell function and secretion of inhibitory cytokines such as IL-10 and TGF-β might underlie Treg function in vivo. The final outcome of autoimmunity vs tolerance depends on the balance between stimulatory signals (Toll-like receptor engagement, costimulation, and antigen dose) and inhibitory signals from Treg. Whereas most Experimental settings analyze the capacity of Treg to prevent onset of Autoimmune Disease, more recent efforts indicate successful treatment of ongoing Disease. Thus, Treg are on the verge of moving from Experimental animal models into clinical applications in humans.
Patrick Matthys - One of the best experts on this subject based on the ideXlab platform.
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defective cd4 cd25 regulatory t cell functioning in collagen induced arthritis an important factor in pathogenesis counter regulated by endogenous ifn γ
Arthritis Research & Therapy, 2005Co-Authors: Hilde Kelchtermans, Bert De Klerck, Tania Mitera, Maarten Van Balen, Dominique Bullens, Alfons Billiau, Georges Leclercq, Patrick MatthysAbstract:Mice with a deficiency in IFN-γ or IFN-γ receptor (IFN-γR) are more susceptible to collagen-induced arthritis (CIA), an Experimental Autoimmune Disease that relies on the use of complete Freund's adjuvant (CFA). Here we report that the heightened susceptibility of IFN-γR knock-out (KO) mice is associated with a functional impairment of CD4+CD25+ Treg cells. Treatment of wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation with collagen type II (CII) significantly accelerated the onset of arthritis and increased the severity of CIA. This is an indication of a role of Treg cells in the effector phase of CIA. IFN-γR deficiency did not affect the number of CD4+CD25+ T cells in the central and peripheral lymphoid tissues. In addition, CD4+CD25+ T cells isolated from naive IFN-γR KO mice had a normal potential to suppress T cell proliferation in vitro. However, after immunisation with CII in CFA, the suppressive activity of CD4+CD25+ T cells became significantly more impaired in IFN-γR-deficient mice. Moreover, expression of the mRNA for Foxp3, a highly specific marker for Treg cells, was lower. We further demonstrated that the effect of endogenous IFN-γ, which accounts for more suppressive activity in wild-type mice, concerns both Treg cells and accessory cells. Our results demonstrate that the decrease in Treg cell activity in CIA is counter-regulated by endogenous IFN-γ.
Cobi Jacoba Johanna Heijnen - One of the best experts on this subject based on the ideXlab platform.
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neonatal dexamethasone treatment increases susceptibility to Experimental Autoimmune Disease in adult rats
Journal of Immunology, 2000Co-Authors: J M Bakker, Annemieke Kavelaars, Patrick Joseph Gerardus Hendrikus Kamphuis, Pieter M Cobelens, H Van Vugt, F Van Bel, Cobi Jacoba Johanna HeijnenAbstract:Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung Disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity ( p ≤ 0.01) and incidence ( p ≤ 0.01) of the inflammatory Autoimmune Disease Experimental Autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to Experimental Autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats ( p ≤ 0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-α and IL-1β in adult life than control rats ( p p p
David A Hafler - One of the best experts on this subject based on the ideXlab platform.
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induction of circulating myelin basic protein and proteolipid protein specific transforming growth factor beta1 secreting th3 t cells by oral administration of myelin in multiple sclerosis patients
Journal of Clinical Investigation, 1996Co-Authors: Hikoaki Fukaura, Howard L Weiner, Sally C Kent, M J Pietrusewicz, Samia J Khoury, David A HaflerAbstract:Oral administration of antigen is a long recognized method of inducing systemic immune tolerance. In animals with Experimental Autoimmune Disease, a major mechanism of oral tolerance triggered by oral administration of antigen involves the induction of regulatory T cells that mediate active suppression by secreting the cytokine TGF-beta 1. Multiple sclerosis (MS) is a presumed T cell-mediated Th1 type Autoimmune Disease. Here, we investigated whether in MS patients oral myelin treatment, containing both myelin basic protein (MBP) and proteolipid protein (PLP), induced antigen specific MBP or PLP reactive T cells that either secreted IL4, TGF-beta1, or alternatively did Th1 type sensitization occur as measured by IFN-gamma secretion. Specifically, 4,860 short-term T cell lines were generated to either MBP, PLP, or tetanus toxoid (TT) from 34 relapsing-remitting MS patients: 17 orally treated with bovine myelin daily for a minimum of 2 yr as compared to 17 nontreated patients. We found a marked increase in the relative frequencies of both MBP and PLP specific TGF-beta1-secreting T cell lines in the myelin treated MS patients as compared to non-treated MS patients (MBP P < 0.001, PLP P < 0.003). In contrast, no change in the frequency of MBP or PLP specific IFN-gamma or TT specific TGF-beta1 secreting T cells were observed. These results suggest that the oral administration of antigens generates antigen specific TGF-beta1 secreting Th3 cells of presumed mucosal origin that represent a distinct lineage of T cells. Since antigen-specific TGF-beta1 secreting cells localize to the target organ and then suppress inflammation in the local microenvironment, oral tolerization with self antigens may provide a therapeutic approach for the treatment of cell-mediated Autoimmune Disease which does not depend upon knowledge of the antigen specificity of the original T cell clone triggering the Autoimmune cascade.
