| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
in Cbl-b–/– Mice
* Department of Medicine, Division of Rheumatic Diseases, and
Center of Immunotherapy for Cancer and Infectious Diseases, University of Connecticut Health Center, Farmington, CT 06030
Cbl-b–/– mice have signaling defects that result in CD28-independent T cell activation, increased IL-2 production, hyper-reactive T cells, and increased autoimmunity. Although the increased autoimmunity in these mice is believed to result from the hyper-reactive T cells, the mechanisms leading from T cell hyper-reactivity to autoimmunity remain unclear. Specifically, the function and interaction of CD4+CD25+ regulatory T cells (Treg) and CD4+CD25– effector T cells (Teff) in Cbl-b–/– mice have not been examined. We now report that Cbl-b–/– CD4+CD25+ Treg exhibit normal regulatory function in vitro. In contrast, the in vitro response of Cbl-b–/– CD4+CD25– Teff is abnormal, in that it is not inhibited by either Cbl-b–/– or wild-type Treg. This resistance of Cbl-b–/– Teff to in vitro regulation is seen at the levels of both DNA synthesis and cell division. In addition to this resistance to CD4+CD25+ Treg, Cbl-b–/– Teff demonstrate in vitro resistance to inhibition by TGF-
. This second form of resistance in Cbl-b–/– Teff is seen despite the expression of normal levels of type II TGF- receptors and normal levels of phosphorylated Smad3 after TGF- stimulation. Coupled with recent reports of resistance to Treg in Teff exposed to LPS-treated dendritic cells, our present findings suggest that resistance to regulation may be a relevant mechanism in both normal immune function and autoimmunity.
This article has been cited by other articles:
|
|
 |
|
  C. M. Cuda, S. Wan, E. S. Sobel, B. P. Croker, and L. Morel Murine Lupus Susceptibility Locus Sle1a Controls Regulatory T Cell Number and Function through Multiple Mechanisms J. Immunol., December 1, 2007; 179(11): 7439 - 7447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Loeser, K. Loser, M. S. Bijker, M. Rangachari, S. H. van der Burg, T. Wada, S. Beissert, C. J.M. Melief, and J. M. Penninger Spontaneous tumor rejection by cbl-b-deficient CD8+ T cells J. Exp. Med., April 16, 2007; 204(4): 879 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Preller, A. Gerber, S. Wrenger, M. Togni, D. Marguet, J. Tadje, U. Lendeckel, C. Rocken, J. Faust, K. Neubert, et al. TGF-beta1-Mediated Control of Central Nervous System Inflammation and Autoimmunity through the Inhibitory Receptor CD26 J. Immunol., April 1, 2007; 178(7): 4632 - 4640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Sukiennicki and D. J. Fowell Distinct Molecular Program Imposed on CD4+ T Cell Targets by CD4+CD25+ Regulatory T Cells J. Immunol., November 15, 2006; 177(10): 6952 - 6961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Wohlfert, L. Gorelik, R. Mittler, R. A. Flavell, and R. B. Clark Cutting Edge: Deficiency in the E3 Ubiquitin Ligase Cbl-b Results in a Multifunctional Defect in T Cell TGF-beta Sensitivity In Vitro and In Vivo J. Immunol., February 1, 2006; 176(3): 1316 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. You, M. Belghith, S. Cobbold, M.-A. Alyanakian, C. Gouarin, S. Barriot, C. Garcia, H. Waldmann, J.-F. Bach, and L. Chatenoud Autoimmune Diabetes Onset Results From Qualitative Rather Than Quantitative Age-Dependent Changes in Pathogenic T-Cells Diabetes, May 1, 2005; 54(5): 1415 - 1422. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
