| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function1
* Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Canada;
Federation of Clinical Immunology Societies Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, and Departments of Microbiology and Immunology, and Medicine, University of Western Ontario, London, Canada; and
Department of Immunology, University of Toronto, Toronto, Canada
TCR
+CD4–CD8– double-negative (DN) T regulatory (Treg) cells have recently been shown to suppress Ag-specific immune responses mediated by CD8+ and CD4+ T cells in humans and mice. Our previous study using cDNA microarray analysis of global gene expression showed that FcR
was the most highly overexpressed gene in functional DN Treg cell clones compared with nonfunctional mutant clones. In this study, we demonstrate that FcR-deficient DN T cells display markedly reduced suppressive activity in vitro. In addition, unlike FcR-sufficient DN T cells, FcR-deficient DN T cells were unable to prolong donor-specific allograft survival when adoptively transferred to recipient mice. Protein analyses indicate that in addition to FcR, DN Treg cell clones also express higher levels of TCR, while mutant clones expressed higher levels of Zap70 and Lck. Within DN Treg cells, we found that FcR associates with the TCR complex and that both FcR and Syk are phosphorylated in response to TCR cross-linking. Inhibition of Syk signaling and FcR expression were both found to reduce the suppressive function of DN Treg cells in vitro. These results indicate that FcR deficiency significantly impairs the ability of DN Treg cells to down-regulate allogeneic immune responses both in vitro and in vivo, and that FcR plays a role in mediating TCR signaling in DN Treg cells.
This article has been cited by other articles:
|
|
 |
|
  C. L. Abram and C. A. Lowell The Expanding Role for ITAM-Based Signaling Pathways in Immune Cells Sci. Signal., March 13, 2007; 2007(377): re2 - re2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kitamura, K. Takeda, T. Koya, N. Miyahara, T. Kodama, A. Dakhama, T. Takai, A. Hirano, M. Tanimoto, M. Harada, et al. Critical Role of the Fc Receptor {gamma}-Chain on APCs in the Development of Allergen-Induced Airway Hyperresponsiveness and Inflammation J. Immunol., January 1, 2007; 178(1): 480 - 488. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
