The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     
 


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Related articles in The JI
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fallarino, F.
Right arrow Articles by Puccetti, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fallarino, F.
Right arrow Articles by Puccetti, P.
The Journal of Immunology, 2006, 176: 6752-6761.
Copyright © 2006 by The American Association of Immunologists

The Combined Effects of Tryptophan Starvation and Tryptophan Catabolites Down-Regulate T Cell Receptor {zeta}-Chain and Induce a Regulatory Phenotype in Naive T Cells1

Francesca Fallarino*, Ursula Grohmann*, Sylvaine You{dagger}, Barbara C. McGrath{ddagger}, Douglas R. Cavener{ddagger}, Carmine Vacca*, Ciriana Orabona*, Roberta Bianchi*, Maria L. Belladonna*, Claudia Volpi*, Pere Santamaria§, Maria C. Fioretti* and Paolo Puccetti2,*

* Department of Experimental Medicine, University of Perugia, Perugia, Italy; {dagger} Institut National de la Santé et de la Recherche Médicale Unité 580-Institut Fédératif de Recherche Necker Enfants-Malades, Hôpital Necker, Paris, France; {ddagger} Department of Biology, The Pennsylvania State University, University Park, PA 16802; and § Julia McFarlane Diabetes Research Centre, University of Calgary, Calgary, Alberta, Canada

Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR {zeta}-chain in murine CD8+ T cells. TCR {zeta} down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan catabolism include the emergence of a regulatory phenotype in naive CD4+CD25 T cells via TGF-beta induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.


Related articles in The JI:

IN THIS ISSUE

The JI 2006 176: 6365-6366. [Full Text]  



This article has been cited by other articles:


Home page
Infect. Immun.Home page
L. Harrington, C. V. Srikanth, R. Antony, S. J. Rhee, A. L. Mellor, H. N. Shi, and B. J. Cherayil
Deficiency of Indoleamine 2,3-Dioxygenase Enhances Commensal-Induced Antibody Responses and Protects against Citrobacter rodentium-Induced Colitis
Infect. Immun., July 1, 2008; 76(7): 3045 - 3053.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
L. Romani, T. Zelante, A. De Luca, F. Fallarino, and P. Puccetti
IL-17 and Therapeutic Kynurenines in Pathogenic Inflammation to Fungi
J. Immunol., April 15, 2008; 180(8): 5157 - 5162.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
M. Razmara, B. Hilliard, A. K. Ziarani, Y. H. Chen, and M. L. Tykocinski
CTLA-4{middle dot}Ig converts naive CD4+CD25- T cells into CD4+CD25+ regulatory T cells
Int. Immunol., April 1, 2008; 20(4): 471 - 483.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
L. K. Jasperson, C. Bucher, A. Panoskaltsis-Mortari, P. A. Taylor, A. L. Mellor, D. H. Munn, and B. R. Blazar
Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality
Blood, March 15, 2008; 111(6): 3257 - 3265.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
C. H. Cook, A. A. Bickerstaff, J.-J. Wang, T. Nadasdy, P. Della Pelle, R. B. Colvin, and C. G. Orosz
Spontaneous Renal Allograft Acceptance Associated with "Regulatory" Dendritic Cells and IDO
J. Immunol., March 1, 2008; 180(5): 3103 - 3112.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer
Natural Regulatory T Cells and Persistent Viral Infection
J. Virol., January 1, 2008; 82(1): 21 - 30.
[Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
J. Li, A. Meinhardt, M.-E. Roehrich, D. Golshayan, J. Dudler, M. Pagnotta, M. Trucco, and G. Vassalli
Indoleamine 2,3-dioxygenase gene transfer prolongs cardiac allograft survival
Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3415 - H3423.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
A. De Luca, C. Montagnoli, T. Zelante, P. Bonifazi, S. Bozza, S. Moretti, C. D'Angelo, C. Vacca, L. Boon, F. Bistoni, et al.
Functional yet Balanced Reactivity to Candida albicans Requires TRIF, MyD88, and IDO-Dependent Inhibition of Rorc
J. Immunol., November 1, 2007; 179(9): 5999 - 6008.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. W. Tas, M. J. Vervoordeldonk, N. Hajji, J. H. N. Schuitemaker, K. F. van der Sluijs, M. J. May, S. Ghosh, M. L. Kapsenberg, P. P. Tak, and E. C. de Jong
Noncanonical NF-{kappa}B signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation
Blood, September 1, 2007; 110(5): 1540 - 1549.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. Metz, J. B. DuHadaway, U. Kamasani, L. Laury-Kleintop, A. J. Muller, and G. C. Prendergast
Novel Tryptophan Catabolic Enzyme IDO2 Is the Preferred Biochemical Target of the Antitumor Indoleamine 2,3-Dioxygenase Inhibitory Compound D-1-Methyl-Tryptophan
Cancer Res., August 1, 2007; 67(15): 7082 - 7087.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
A. P. J. van der Marel, J. N. Samsom, M. Greuter, L. A. van Berkel, T. O'Toole, G. Kraal, and R. E. Mebius
Blockade of IDO Inhibits Nasal Tolerance Induction
J. Immunol., July 15, 2007; 179(2): 894 - 900.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
H. Hamdi, V. Godot, M.-C. Maillot, M. V. Prejean, N. Cohen, R. Krzysiek, F. M. Lemoine, W. Zou, and D. Emilie
Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper
Blood, July 1, 2007; 110(1): 211 - 219.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Z. Zhang, C. L. Gorman, A.-C. Vermi, C. Monaco, A. Foey, S. Owen, P. Amjadi, A. Vallance, C. McClinton, F. Marelli-Berg, et al.
TCR{zeta}dimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues
Blood, May 15, 2007; 109(10): 4328 - 4335.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Boasso, J.-P. Herbeuval, A. W. Hardy, S. A. Anderson, M. J. Dolan, D. Fuchs, and G. M. Shearer
HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells
Blood, April 15, 2007; 109(8): 3351 - 3359.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
E. Larrea, J. I. Riezu-Boj, L. Gil-Guerrero, N. Casares, R. Aldabe, P. Sarobe, M. P. Civeira, J. L. Heeney, C. Rollier, B. Verstrepen, et al.
Upregulation of Indoleamine 2,3-Dioxygenase in Hepatitis C Virus Infection
J. Virol., April 1, 2007; 81(7): 3662 - 3666.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
Z. Liu, H. Dai, N. Wan, T. Wang, S. Bertera, M. Trucco, and Z. Dai
Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism
J. Immunol., April 1, 2007; 178(7): 4260 - 4266.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Curti, S. Pandolfi, B. Valzasina, M. Aluigi, A. Isidori, E. Ferri, V. Salvestrini, G. Bonanno, S. Rutella, I. Durelli, et al.
Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells
Blood, April 1, 2007; 109(7): 2871 - 2877.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2006 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2006 by The American Association of Immunologists, Inc. All rights reserved.