| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101
The development and maintenance of T regulatory (Treg) cells critically depend on IL-2. This requirement for IL-2 might be due to specificity associated with IL-2R signal transduction or because IL-2 was uniquely present in the niche in which Treg cells reside. To address this issue, we examined the capacity of IL-7R-dependent signaling to support Treg cell production and prevent autoimmunity in IL-2R
–/– mice. Expression of transgenic wild-type IL-7R or a chimeric receptor that consisted of the extracytoplasmic domain of the IL-7R 
-chain and the cytoplasmic domain of IL-2R -chain in IL-2R–/– mice did not prevent autoimmunity. Importantly, expression of a chimeric receptor that consisted of the extracytoplasmic domain of the IL-2R -chain and the cytoplasmic domain of IL-7R -chain in IL-2R–/– mice led to Treg cells production in the thymus and periphery and prevented autoimmunity. Signaling through the IL-2R or chimeric IL-2R/IL-7R in vivo or the culture of thymocytes from IL-2R–/– mice with IL-7 led to up-regulation of Foxp3 and CD25 on Treg cells. These findings indicate that IL-7R signal transduction is competent to promote Treg cell production, but this signaling requires triggering through IL-2 by binding to the extracytoplasmic portion of the IL-2R via this chimeric receptor. Thus, a major factor controlling the nonredundant activity of the IL-2R is selective compartmentalization of IL-2-producing cells with Treg cells in vivo.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants RO1-CA45957 and RO1-AI055815 from the National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Thomas R. Malek, Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, PO Box 016960, Miami, FL 33101. E-mail address: tmalek{at}med.miami.edu
3 Abbreviations used in this paper: 
c, common -chain; DN, double negative; DP, double positive; Treg; T regulatory; MFI, mean fluorescence intensity.
This article has been cited by other articles:
|
|
 |
|
  M. S. Wilson, J. T. Pesce, T. R. Ramalingam, R. W. Thompson, A. Cheever, and T. A. Wynn Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells J. Immunol., November 15, 2008; 181(10): 6942 - 6954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mazzucchelli, J. A. Hixon, R. Spolski, X. Chen, W. Q. Li, V. L. Hall, J. Willette-Brown, A. A. Hurwitz, W. J. Leonard, and S. K. Durum Development of regulatory T cells requires IL-7R{alpha} stimulation by IL-7 or TSLP Blood, October 15, 2008; 112(8): 3283 - 3292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Bayer, J. Y. Lee, A. de la Barrera, C. D. Surh, and T. R. Malek A Function for IL-7R for CD4+CD25+Foxp3+ T Regulatory Cells J. Immunol., July 1, 2008; 181(1): 225 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 The International Multiple Sclerosis Genetics Cons Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study N. Engl. J. Med., August 30, 2007; 357(9): 851 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Sanchez-Guajardo, C. Tanchot, J. T. O'Malley, M. H. Kaplan, S. Garcia, and A. A. Freitas Agonist-Driven Development of CD4+CD25+Foxp3+ Regulatory T Cells Requires a Second Signal Mediated by Stat6 J. Immunol., June 15, 2007; 178(12): 7550 - 7556. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
