Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
free free
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll Immunoregulatory pathways controlling progression of autoimmunity in NOD mice You S; Alyanakian MA; Segovia B; Damotte D; Bluestone J; Bach JF; Chatenoud LAnn N Y Acad Sci 2008[Dec]; 1150 (ä): 300-10The activation, expansion, and survival of regulatory T cells (Tregs) as well as the expression of their suppressive capacities result from distinct signaling pathways involving various membrane receptors and cytokines. Multiple studies have shown that thymus-derived naturally occurring Tregs constitutively express the forkhead/winged helix transcription factor FoxP3 in addition to high levels of CD25, the negative co-stimulatory molecule CTLA-4, and the glucocorticoid-induced TNF receptor-related protein GITR. At variance, adaptive or induced Tregs acquire these phenotypic markers as they differentiate in the periphery, following adequate stimulation in the appropriate environment, together with their capacity to produce immunomodulatory cytokines (mainly, IL-4, IL-10 and TGF-beta) and to display regulatory capacities. However, none of these molecules but FoxP3 are restricted to Tregs since they may also be expressed and upregulated on activated effector T cells. This explains why different hypotheses were proposed to interpret interesting reports showing that in vivo abrogation of CTLA-4 signaling using neutralizing CTLA-4 antibodies triggers different autoimmune or immune-mediated manifestations. Thus, an effect on pathogenic T cell effectors and/or Tregs has been proposed. Here we present and discuss recent results we obtained in the nonobese diabetic (NOD) mouse model of spontaneous autoimmune diabetes, arguing for a key role of CTLA-4 in the functional activity of Tregs. Moreover, data are presented that simultaneous blockade of CTLA4 and TGF-beta further impairs immunoregulatory circuits that control disease progression.|Animals[MESH]|Antigens, CD/immunology/physiology[MESH]|Autoimmunity/*immunology[MESH]|CTLA-4 Antigen[MESH]|Diabetes Mellitus, Type 1/complications/*immunology[MESH]|Disease Progression[MESH]|Homeostasis/immunology[MESH]|Immune Tolerance/*physiology[MESH]|Mice[MESH]|Mice, Inbred NOD[MESH]|Signal Transduction/*immunology[MESH]|Systemic Inflammatory Response Syndrome/etiology/pathology[MESH]|T-Lymphocytes, Regulatory/*physiology[MESH]|Transforming Growth Factor beta/physiology[MESH] |