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Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305
Recently, CD4+CD25+ T cells have been
implicated in the control of diabetes, suggesting that the inflamed
islets of Langerhans in prediabetic NOD mice are under peripheral
immune surveillance. Here we show that
CD4+CD25+ splenocytes inhibit diabetes in
cotransfer with islet-infiltrating cells. Furthermore, CD62L expression
is necessary for this disease-delaying effect of
CD4+CD25+ cells in vivo, but not for their
suppressor function in vitro. We demonstrate that the
CD4+CD25+CD62L+ splenocytes express
CCR7 at high levels and migrate toward secondary lymphoid tissue
chemokine and ELC (macrophage-inflammatory protein-3
), lymphoid
chemokines, whereas
CD4+CD25+CD62L- splenocytes
preferentially express CCR2, CCR4, and CXCR3 and migrate toward the
corresponding inflammatory chemokines. These data demonstrate that
CD4+CD25+CD62L+, but not
CD4+CD25+CD62L-, splenocytes delay
diabetes transfer, and that CD4+CD25+
suppressor T cells are comprised of at least two subpopulations that
behave differently in cotransfer in vivo and express distinct chemokine
receptor and chemotactic response profiles despite demonstrating
equivalent suppressor functions in vitro.
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M. Afanasyeva, D. Georgakopoulos, D. F. Belardi, D. Bedja, D. Fairweather, Y. Wang, Z. Kaya, K. L. Gabrielson, E. R. Rodriguez, P. Caturegli, et al. Impaired up-regulation of CD25 on CD4+ T cells in IFN-{gamma} knockout mice is associated with progression of myocarditis to heart failure PNAS, January 4, 2005; 102(1): 180 - 185. [Abstract] [Full Text] [PDF]
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S. Liang, P. Alard, Y. Zhao, S. Parnell, S. L. Clark, and M. M. Kosiewicz Conversion of CD4+ CD25- cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus J. Exp. Med., January 3, 2005; 201(1): 127 - 137. [Abstract] [Full Text] [PDF]
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R. K. Gregg, R. Jain, S. J. Schoenleber, R. Divekar, J. J. Bell, H.-H. Lee, P. Yu, and H. Zaghouani A Sudden Decline in Active Membrane-Bound TGF-{beta} Impairs Both T Regulatory Cell Function and Protection against Autoimmune Diabetes J. Immunol., December 15, 2004; 173(12): 7308 - 7316. [Abstract] [Full Text] [PDF]
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P. A. Taylor, A. Panoskaltsis-Mortari, J. M. Swedin, P. J. Lucas, R. E. Gress, B. L. Levine, C. H. June, J. S. Serody, and B. R. Blazar L-Selectinhi but not the L-selectinlo CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection Blood, December 1, 2004; 104(12): 3804 - 3812. [Abstract] [Full Text] [PDF]
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W. Yang, S. Hussain, Q.-S. Mi, P. Santamaria, and T. L. Delovitch Perturbed Homeostasis of Peripheral T Cells Elicits Decreased Susceptibility to Anti-CD3-Induced Apoptosis in Prediabetic Nonobese Diabetic Mice J. Immunol., October 1, 2004; 173(7): 4407 - 4416. [Abstract] [Full Text] [PDF]
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D. Yadav, V. Judkowski, M. Flodstrom-Tullberg, L. Sterling, W. L. Redmond, L. Sherman, and N. Sarvetnick B7-2 (CD86) Controls the Priming of Autoreactive CD4 T Cell Response against Pancreatic Islets J. Immunol., September 15, 2004; 173(6): 3631 - 3639. [Abstract] [Full Text] [PDF]
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N. Sarween, A. Chodos, C. Raykundalia, M. Khan, A. K. Abbas, and L. S. K. Walker CD4+CD25+ Cells Controlling a Pathogenic CD4 Response Inhibit Cytokine Differentiation, CXCR-3 Expression, and Tissue Invasion J. Immunol., September 1, 2004; 173(5): 2942 - 2951. [Abstract] [Full Text] [PDF]
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N. Giarratana, G. Penna, S. Amuchastegui, R. Mariani, K. C. Daniel, and L. Adorini A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development J. Immunol., August 15, 2004; 173(4): 2280 - 2287. [Abstract] [Full Text] [PDF]
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P. Hoffmann, R. Eder, L. A. Kunz-Schughart, R. Andreesen, and M. Edinger Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells Blood, August 1, 2004; 104(3): 895 - 903. [Abstract] [Full Text] [PDF]
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S. Mendez, S. K. Reckling, C. A. Piccirillo, D. Sacks, and Y. Belkaid Role for CD4+ CD25+ Regulatory T Cells in Reactivation of Persistent Leishmaniasis and Control of Concomitant Immunity J. Exp. Med., July 19, 2004; 200(2): 201 - 210. [Abstract] [Full Text] [PDF]
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M. Stassen, H. Jonuleit, C. Muller, M. Klein, C. Richter, T. Bopp, S. Schmitt, and E. Schmitt Differential Regulatory Capacity of CD25+ T Regulatory Cells and Preactivated CD25+ T Regulatory Cells on Development, Functional Activation, and Proliferation of Th2 Cells J. Immunol., July 1, 2004; 173(1): 267 - 274. [Abstract] [Full Text] [PDF]
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K. V. Tarbell, S. Yamazaki, K. Olson, P. Toy, and R. M. Steinman CD25+ CD4+ T Cells, Expanded with Dendritic Cells Presenting a Single Autoantigenic Peptide, Suppress Autoimmune Diabetes J. Exp. Med., June 7, 2004; 199(11): 1467 - 1477. [Abstract] [Full Text] [PDF]
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N. A. Danke, D. M. Koelle, C. Yee, S. Beheray, and W. W. Kwok Autoreactive T Cells in Healthy Individuals J. Immunol., May 15, 2004; 172(10): 5967 - 5972. [Abstract] [Full Text] [PDF]
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V. Viglietta, C. Baecher-Allan, H. L. Weiner, and D. A. Hafler Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis J. Exp. Med., April 5, 2004; 199(7): 971 - 979. [Abstract] [Full Text] [PDF]
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F. J. Clark, R. Gregg, K. Piper, D. Dunnion, L. Freeman, M. Griffiths, G. Begum, P. Mahendra, C. Craddock, P. Moss, et al. Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells Blood, March 15, 2004; 103(6): 2410 - 2416. [Abstract] [Full Text] [PDF]
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J. Huehn, K. Siegmund, J. C.U. Lehmann, C. Siewert, U. Haubold, M. Feuerer, G. F. Debes, J. Lauber, O. Frey, G. K. Przybylski, et al. Developmental Stage, Phenotype, and Migration Distinguish Naive- and Effector/Memory-like CD4+ Regulatory T Cells J. Exp. Med., February 2, 2004; 199(3): 303 - 313. [Abstract] [Full Text] [PDF]
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L. A. Stephens, A. N. Barclay, and D. Mason Phenotypic characterization of regulatory CD4+CD25+ T cells in rats Int. Immunol., February 1, 2004; 16(2): 365 - 375. [Abstract] [Full Text] [PDF]
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M.-A. Alyanakian, S. You, D. Damotte, C. Gouarin, A. Esling, C. Garcia, S. Havouis, L. Chatenoud, and J.-F. Bach Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases PNAS, December 23, 2003; 100(26): 15806 - 15811. [Abstract] [Full Text] [PDF]
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S. Gregori, N. Giarratana, S. Smiroldo, and L. Adorini Dynamics of Pathogenic and Suppressor T Cells in Autoimmune Diabetes Development J. Immunol., October 15, 2003; 171(8): 4040 - 4047. [Abstract] [Full Text] [PDF]
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S. Fisson, G. Darrasse-Jeze, E. Litvinova, F. Septier, D. Klatzmann, R. Liblau, and B. L. Salomon Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State J. Exp. Med., September 2, 2003; 198(5): 737 - 746. [Abstract] [Full Text] [PDF]
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G. Rajagopalan, Y. C. Kudva, L. Chen, L. Wen, and C. S. David Autoimmune diabetes in HLA-DR3/DQ8 transgenic mice expressing the co-stimulatory molecule B7-1 in the {beta} cells of islets of Langerhans Int. Immunol., September 1, 2003; 15(9): 1035 - 1044. [Abstract] [Full Text] [PDF]
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K. S. Goudy, B. R. Burkhardt, C. Wasserfall, S. Song, M. L. Campbell-Thompson, T. Brusko, M. A. Powers, M. J. Clare-Salzler, E. S. Sobel, T. M. Ellis, et al. Systemic Overexpression of IL-10 Induces CD4+CD25+ Cell Populations In Vivo and Ameliorates Type 1 Diabetes in Nonobese Diabetic Mice in a Dose-Dependent Fashion J. Immunol., September 1, 2003; 171(5): 2270 - 2278. [Abstract] [Full Text] [PDF]
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T. Mizobuchi, K. Yasufuku, Y. Zheng, M. A. Haque, K. M. Heidler, K. Woods, G. N. Smith Jr., O. W. Cummings, T. Fujisawa, J. S. Blum, et al. Differential Expression of Smad7 Transcripts Identifies the CD4+CD45RChigh Regulatory T Cells That Mediate Type V Collagen-Induced Tolerance to Lung Allografts J. Immunol., August 1, 2003; 171(3): 1140 - 1147. [Abstract] [Full Text] [PDF]
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