toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author Sather, B.D.; Treuting, P.; Perdue, N.; Miazgowicz, M.; Fontenot, J.D.; Rudensky, A.Y.; Campbell, D.J. url  openurl
  Title Altering the distribution of Foxp3+ regulatory T cells results in tissue-specific inflammatory disease Type Journal Article
  Year 2007 Publication J Exp Med Abbreviated Journal  
  Volume Issue Pages  
  Keywords  
  Abstract CD4(+)Foxp3(+) regulatory T cells (T reg) are essential for maintaining self-tolerance, but their functional mechanisms and sites of action in vivo are poorly defined. We examined the homing receptor expression and tissue distribution of T reg cells in the steady state and determined whether altering their distribution by removal of a single chemokine receptor impairs their ability to maintain tissue-specific peripheral tolerance. We found that T reg cells are distributed throughout all nonlymphoid tissues tested, and are particularly prevalent in the skin, where they express a unique CCR4(+)CD103(hi) phenotype. T reg cell expression of CCR4 and CD103 is induced by antigen-driven activation within subcutaneous lymph nodes, and accumulation of T reg cells in the skin and lung airways is impaired in the absence of CCR4 expression. Mice with a complete loss of CCR4 in the T reg cell compartment develop lymphocytic infiltration and severe inflammatory disease in the skin and lungs, accompanied by peripheral lymphadenopathy and increased differentiation of skin-tropic CD4(+)Foxp3(-) T cells. Thus, selectively altering T reg cell distribution in vivo leads to the development of tissue-specific inflammatory disease.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Benaroya Research Institute, Seattle, WA 98101. Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Sather2007 Serial 75  
Permanent link to this record
 

 
Author Fathman, C.G.; Soares, L.; Chan, S.M.; Utz, P.J. url  openurl
  Title An array of possibilities for the study of autoimmunity Type Journal Article
  Year 2005 Publication Nature Abbreviated Journal  
  Volume 435 Issue 7042 Pages 605-611  
  Keywords  
  Abstract Since the completion of the sequencing of the human genome, scientific focus has shifted from studying genes to analysing the much larger number of proteins encoded by them. Several proteins can be generated from a single gene depending on how the genetic information is read (transcribed) and how the resultant protein is modified following translation (post-translational modification). Genomic and proteomic technologies are already providing useful information about autoimmune disease, and they are likely to lead to important discoveries within the next decade.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medic Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Fathman2005 Serial 76  
Permanent link to this record
 

 
Author Khattri, R.; Cox, T.; Yasayko, S.A.; Ramsdell, F. url  openurl
  Title An essential role for Scurfin in CD4+CD25+ T regulatory cells Type Journal Article
  Year 2003 Publication Nat Immunol Abbreviated Journal  
  Volume 4 Issue 4 Pages 337-342  
  Keywords Animals; Antigens, Differentiation/genetics/metabolism; CD4-Positive T-Lymphocytes/immunology/*metabolism; DNA-Binding Proteins/genetics/*immunology/*metabolism; *Immunoconjugates; Interleukin-10/metabolism; Mice; Mice, Transgenic; Receptors, Interleukin-2/immunology/*metabolism; Receptors, Nerve Growth Factor/metabolism; Receptors, Tumor Necrosis Factor/metabolism; Transforming Growth Factor beta/metabolism  
  Abstract The molecular properties that characterize CD4+CD25+ regulatory T cells (TR cells) remain elusive. Absence of the transcription factor Scurfin (also known as forkhead box P3 and encoded by Foxp3) causes a rapidly fatal lymphoproliferative disease, similar to that seen in mice lacking cytolytic T lymphocyte-associated antigen 4 (CTLA-4). Here we show that Foxp3 is highly expressed by T(R) cells and is associated with T(R) cell activity and phenotype. Scurfin-deficient mice lack T(R) cells, whereas mice that overexpress Foxp3 possess more T(R) cells. In Foxp3-overexpressing mice, both CD4+CD25- and CD4-CD8+ T cells show suppressive activity and CD4+CD25- cells express glucocorticoid-induced tumor-necrosis factor receptor-related (GITR) protein. The forced expression of Foxp3 also delays disease in CTLA-4-/- mice, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the T(R) cell lineage.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Celltech R&D Inc., 1631 220th Street SE, Bothell, Washington 98021, USA. Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes 1529-2908Journal Article Approved no  
  Call Number MRC @ kga @ Khattri2003 Serial 77  
Permanent link to this record
 

 
Author Brusko, T.M.; Wasserfall, C.H.; Agarwal, A.; Kapturczak, M.H.; Atkinson, M.A. url  openurl
  Title An integral role for heme oxygenase-1 and carbon monoxide in maintaining peripheral tolerance by CD4+CD25+ regulatory T cells Type Journal Article
  Year 2005 Publication J Immunol Abbreviated Journal  
  Volume 174 Issue 9 Pages 5181-5186  
  Keywords Animals; Carbon Monoxide/*physiology; Cell Communication/*immunology; Heme Oxygenase (Decyclizing)/*physiology; Humans; *Immune Tolerance; Receptors, Interleukin-2/*biosynthesis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; T-Lymphocytes, Suppressor-Inducer/*enzymology/*immunology/metabolism  
  Abstract Over the past decade, a great deal of interest and attention has been directed toward a population of regulatory T cells (Treg) coexpressing the markers CD4 and CD25. The hallmark phenotype of this cell population resides in its ability to dominantly maintain peripheral tolerance and avert autoimmunity. Despite robust research interest in Treg, their mechanism of action and interaction with other cell populations providing immune regulation remains unclear. In this study, we present a model for Treg activity that implicates carbon monoxide, a by-product of heme oxygenase-1 activity, as an important and underappreciated facet in the suppressive capacity of Treg. Our hypothesis is based on recent evidence supporting a role for heme oxygenase-1 in regulating immune reactivity and posit carbon monoxide to function as a suppressive molecule. Potential roles for indoleamine 2,3-dioxygenase, costimulatory molecules, and cytokines in tolerance induction are also presented. This model, if validated, could act as a catalyst for new investigations into Treg function and ultimately result in novel methods to modulate Treg biology toward therapeutic applications.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes 0022-1767Journal ArticleReviewReview, Tutorial Approved no  
  Call Number MRC @ kga @ Brusko2005 Serial 78  
Permanent link to this record
 

 
Author Hsieh, C.S.; Zheng, Y.; Liang, Y.; Fontenot, J.D.; Rudensky, A.Y. url  openurl
  Title An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires Type Journal Article
  Year 2006 Publication Nat Immunol Abbreviated Journal  
  Volume 7 Issue 4 Pages 401-410  
  Keywords  
  Abstract The relationship between the T cell receptor (TCR) repertoires used by self-reactive transcription factor Foxp3-positive (Foxp3(+)) CD4(+) regulatory T cells (T(reg) cells) and nonregulatory T cells with autoimmune potential is unclear. Here we found that the TCR repertoire of thymic T(reg) cells in TCRbeta-transgenic mice was diverse and was more similar to that of peripheral T(reg) cells than that of nonregulatory T cells, suggesting that thymic T(reg) cells make a substantial contribution to the peripheral T(reg) cell population. Activated T cells in Foxp3-deficient mice, which lack T(reg) cells, 'preferentially' used TCRs found in the TCR repertoire of T(reg) cells in Foxp3-sufficient TCRbeta-transgenic mice, suggesting that these self-reactive TCRs contribute to the pathology of Foxp3-deficient mice. Our analyses suggest that T(reg) cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Medicine and Division of Rheumatology, University of Washington, Seattle, Washington 9 Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Hsieh2006 Serial 79  
Permanent link to this record
 

 
Author Tellier, J.; van Meerwijk, J.P.; Romagnoli, P. url  openurl
  Title An MHC-linked locus modulates thymic differentiation of CD4+CD25+Foxp3+ regulatory T lymphocytes Type Journal Article
  Year 2006 Publication Int Immunol Abbreviated Journal  
  Volume 18 Issue 11 Pages 1509-1519  
  Keywords  
  Abstract CD4(+)CD25(+)Foxp3(+) regulatory T lymphocytes are crucial for maintenance of immunological tolerance to self and innocuous non-self, are known to modulate immunity to tumors and infectious agents and can induce transplantation tolerance. Surprisingly, only a single genetic polymorphism is known to modulate regulatory T cell (Treg) development in the thymus, leading to a lethal autoimmune disorder. Here, we show that considerably different levels of Tregs are found in the thymi of distinct common laboratory mouse strains. We demonstrate that distinct levels of phenotypically and functionally identical Tregs develop with similar kinetics in the studied mice, that the responsible locus acts in a thymocyte-intrinsic manner and that levels of thymic Foxp3(+) Tregs correlate to those found in the periphery. Using several congenic mouse strains, we mapped one of the at least two genetic loci capable of quantitatively modulating thymic Treg development to a </=2.2 Mb region telomeric to the MHC. Our data indicate that polymorphic genes closely linked to the MHC locus substantially modulate differentiation of Tregs. Identification of responsible genes should help in understanding the mechanisms involved in commitment to the Treg lineage as well as selection of these cells in the thymus.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Tolerance and Autoimmunity section, Centre de Physiopathologie de Toulouse Purpan, Institut National Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Tellier2006 Serial 80  
Permanent link to this record
 

 
Author Abramson, J.; Xu, R.; Pecht, I. url  openurl
  Title An unusual inhibitory receptor--the mast cell function-associated antigen (MAFA) Type Journal Article
  Year 2002 Publication Mol Immunol Abbreviated Journal  
  Volume 38 Issue 16-18 Pages 1307-1313  
  Keywords  
  Abstract The mast cell function-associated antigen (MAFA) is a type II membranal glycoprotein that was first identified on the surface of rat mucosal-type mast cells of the RBL-2H3 line. A C-type lectin domain and an immunoreceptor tyrosine-based inhibitory motif (ITIM) are located in the extracellular and intracellular domains of MAFA, respectively. Human and mouse homologues of MAFA have been discovered recently. However, they are expressed also or only by NK and T-cells, where they most probably play different roles. MAFA clustering by its specific antibody mAb G63 has been previously shown to cause a dose-dependent inhibition of the secretory response of these cells to the FcepsilonRI stimulus. More recent results established that MAFA's inhibitory action involves at least two different enzymes: Following the tyrosyl-phosphorylation of MAFA ITIM by the PTK Lyn, two phosphatases SHIP and SHP2 are recruited to it at the plasma membrane where they propagate the inhibitory signals. The following is a brief report on this unusual inhibitory receptor and its functional activities.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel. Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Abramson2002 Serial 81  
Permanent link to this record
 

 
Author Lopes, J.E.; Torgerson, T.R.; Schubert, L.A.; Anover, S.D.; Ocheltree, E.L.; Ochs, H.D.; Ziegler, S.F. url  openurl
  Title Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor Type Journal Article
  Year 2006 Publication J Immunol Abbreviated Journal  
  Volume 177 Issue 5 Pages 3133-3142  
  Keywords  
  Abstract Foxp3 has been shown to be both necessary and sufficient for the development and function of naturally arising CD4+ CD25+ regulatory T cells in mice. Mutation of Foxp3 in Scurfy mice and FOXP3 in humans with IPEX results in fatal, early onset autoimmune disease and demonstrates the critical role of FOXP3 in maintaining immune homeostasis. The FOXP3 protein encodes several functional domains, including a C2H2 zinc finger, a leucine zipper, and a winged-helix/forkhead (FKH) domain. We have shown previously that FOXP3 functions as a transcriptional repressor and inhibits activation-induced IL-2 gene transcription. To characterize the role of each predicted functional domain on the in vivo activity of FOXP3, we have evaluated the location of point mutations identified in a large cohort of patients with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) and found them to cluster primarily within the FKH domain and the leucine zipper, but also present within the poorly defined N-terminal portion of the protein. The molecular functions of each of the IPEX-targeted domains were investigated. We show that FOXP3 is constitutively localized to the nucleus and this localization requires sequences at both the amino and C-terminal ends of its FKH domain. Moreover, FOXP3 was found to homodimerize through its leucine zipper. We also identify a novel functional domain within the N-terminal half of FOXP3, which is required for FOXP3-mediated repression of transcription from both a constitutively active and a NF-AT-inducible promoter. Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Benaroya Research Institute, Virginia Mason, Seattle, WA 98101, USA. Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Lopes2006 Serial 82  
Permanent link to this record
 

 
Author Sakaguchi, S.; Sakaguchi, N. url  openurl
  Title Animal models of arthritis caused by systemic alteration of the immune system Type Journal Article
  Year 2005 Publication Curr Opin Immunol Abbreviated Journal  
  Volume 17 Issue 6 Pages 589-594  
  Keywords  
  Abstract Animal models are instrumental in understanding the etiology and pathogenetic mechanisms of rheumatoid arthritis. Several new mouse models have either been produced, including transgenics, gene-knockouts, and gene knock-ins, or established as a spontaneous disease due to natural gene mutations. These models are suitable for addressing the roles of T cells, autoantibodies, cytokines and innate immunity in the development and progression of rheumatoid arthritis. In particular, they now provide insights into how systemic alterations of the immune system result in a local development of chronic arthritis that leads to joint destruction.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyo Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Sakaguchi2005 Serial 83  
Permanent link to this record
 

 
Author Nadkarni, S.; Mauri, C.; Ehrenstein, M.R. url  openurl
  Title Anti-TNF-{alpha} therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-{beta} Type Journal Article
  Year 2007 Publication J Exp Med Abbreviated Journal  
  Volume Issue Pages  
  Keywords  
  Abstract The induction of regulatory T (T reg) cells holds considerable potential as a treatment for autoimmune diseases. We have previously shown that CD4(+)CD25(hi) T reg cells isolated from patients with active rheumatoid arthritis (RA) have a defect in their ability to suppress proinflammatory cytokine production by CD4(+)CD25(+) T cells. This defect, however, was overcome after anti-tumor necrosis factor (TNF)-alpha antibody (infliximab) therapy. Here, we demonstrate that infliximab therapy gives rise to a CD4(+)CD25(hi)FoxP3(+) T reg cell population, which mediates suppression via transforming growth factor (TGF)-beta and interleukin 10, and lacks CD62L expression, thereby distinguishing this T reg cell subset from natural T reg cells present in healthy individuals and patients with active RA. In vitro, infliximab induced the differentiation of CD62L(-) T reg cells from CD4(+)CD25(-) T cells isolated from active RA patients, a process dependent on TGF-beta. In spite of the potent suppressor capacity displayed by this CD62L(-) T reg cell population, the natural CD62L(+) T reg cells remained defective in infliximab-treated patients. These results suggest that anti-TNF-alpha therapy in RA patients generates a newly differentiated population of T reg cells, which compensates for the defective natural T reg cells. Therefore, manipulation of a proinflammatory environment could represent a therapeutic strategy for the induction of T reg cells and the restoration of tolerance.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Centre For Rheumatology, Department of Medicine, Windeyer Institute, University College London, Lond Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number MRC @ kga @ Nadkarni2007 Serial 84  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: