| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Molecular Immunology Unit and
Lymphocyte Population Biology Unit, Department of Immunology, Institut Pasteur, Paris, France; and
Institute of Immunology, Medical University of Vienna, Vienna Competence Center, Vienna, Austria
Adaptation of the T cell activation threshold may be one mechanism to control autoreactivity. To investigate its occurrence in vivo, we engineered a transgenic mouse model with increased TCR-dependent excitability by expressing a Zap70 gain-of-function mutant (ZAP-YEEI) in postselection CD8 thymocytes and T cells. Increased basal phosphorylation of the Zap70 substrate linker for activation of T cells was detected in ZAP-YEEI-bearing CD8 T cells. However, these cells were not activated, but had reduced levels of TCR and CD5. Moreover, they produced lower cytokine amounts and showed faster dephosphorylation of linker for activation of T cells and ERK upon activation. Normal TCR levels and cytokine production were restored by culturing cells in the absence of TCR/spMHC interaction, demonstrating dynamic tuning of peripheral T cell responses. The effect of avidity for self-ligand(s) on this sensory adaptation was studied by expressing ZAP-YEEI in P14 or HY TCR transgenic backgrounds. Unexpectedly, double-transgenic animals expressed ZAP-YEEI prematurely in double-positive thymocytes, but no overt alteration of selection processes was observed. Instead, modifications of TCR and CD5 expression due to ZAP-YEEI suggested that signal tuning occurred during thymic maturation. Importantly, although P14 x ZAP-YEEI peripheral CD8 T cells were reduced in number and showed lower Ag-induced cytokine production and limited lymphopenia-driven proliferation, the peripheral survival/expansion and Ag responsiveness of HY x ZAP-YEEI cells were enhanced. Our data provide support for central and peripheral sensory T cell adaptation induced as a function of TCR avidity for self-ligands and signaling level. This may contribute to buffer excessive autoreactivity while optimizing TCR repertoire usage.
This article has been cited by other articles:
|
|
 |
|
  U. Koelsch, B. Schraven, and L. Simeoni SIT and TRIM Determine T Cell Fate in the Thymus J. Immunol., November 1, 2008; 181(9): 5930 - 5939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gil, A. G. Schrum, M. A. Daniels, and E. Palmer A Role for CD8 in the Developmental Tuning of Antigen Recognition and CD3 Conformational Change J. Immunol., March 15, 2008; 180(6): 3900 - 3909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Posevitz, B. Arndt, T. Krieger, N. Warnecke, B. Schraven, and L. Simeoni Regulation of T Cell Homeostasis by the Transmembrane Adaptor Protein SIT J. Immunol., February 1, 2008; 180(3): 1634 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. D. Bartolo, B. Montagne, M. Salek, B. Jungwirth, F. Carrette, J. Fourtane, N. Sol-Foulon, F. Michel, O. Schwartz, W. D. Lehmann, et al. A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76 J. Exp. Med., March 19, 2007; 204(3): 681 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dong, B. Corre, E. Foulon, E. Dufour, A. Veillette, O. Acuto, and F. Michel T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2 J. Exp. Med., October 30, 2006; 203(11): 2509 - 2518. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
