| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* The Edward Jenner Institute for Vaccine Research, University of Oxford, Compton, United Kingdom;
Institut National de la Santé et de la Recherche Médicale UMRS 872, Université René Descartes (Paris-5) and Université Pierre et Marie Curie (Paris-6), Equipe 16-Immunopathology and Therapeutic Intervention Centre de Recherche des Cordeliers, Paris, France; and
Faculté de Pharmacie, Universite Paris-Sud, Châtenay-Malabry, France
Interactions between dendritic cells (DC) and T cells are known to involve the delivery of signals in both directions. We sought to characterize the effects on human DC of contact with different subsets of activated CD4+ T cells. The results showed that interaction with CD25highCD4+ regulatory T cells (Tregs) caused DC to take on very different properties than contact with naive or memory phenotype T cells. Whereas non-Tregs stimulated DC maturation, culture with Tregs produced DC with a mixed phenotype. By many criteria, Tregs inhibited DC maturation, inducing down-regulation of costimulatory molecules and T cell stimulatory activity. However, DC exposed to Tregs also showed some changes typically associated with DC maturation, namely, increased expression of CCR7 and MHC class II molecules, and gained the ability to migrate in response to the CCR7 ligand CCL19. Both soluble factors and cell-associated molecules were shown to be involved in Treg modulation of DC, with lymphocyte activation gene 3 (LAG-3) playing a predominant role in driving maturation-associated changes. The data show that Tregs induce the generation of semimature DC with the potential to migrate into lymphoid organs, suggesting a possible mechanism by which Tregs down-modulate immune responses.
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 from The Edward Jenner Institute for Vaccine Research, U.K. (to J.B. and D.F.T.), and Institut National de la Santé et de la Recherche Médicale and Centre National de la Recherche Scientifique, France, and UPMC-Paris VI, France (to J.B. and S.V.K.).
2 Address correspondence and reprint requests to Dr. Jagadeesh Bayry, Institut National de la Santé et de la Recherche Medicalé UMRS 872, Université René Descartes (Paris-5) and Université Pierre et Marie Curie (Paris-6), Equipe 16-Immunopathology and Therapeutic Intervention Centre de Recherche des Cordeliers, 15, rue de l’Ecole de Médecine, Paris, France. E-mail address: jagadeesh.bayry{at}umrs681.jussieu.fr or Dr. David F. Tough, Group Head, T Cell Regulation, Target Discovery, RI CEDD, GlaxoSmithKline, Gunnels Wood Road, Stevenage, U.K. E-mail address: david.f.tough{at}gsk.com
3 Current address: Target Discovery, RI CEDD, GlaxoSmithKline, Gunnels Wood Road, Stevenage, U.K.
4 Abbreviations used in this paper: LAG-3, lymphocyte activation gene 3; DC, dendritic cell; CD40L, CD40 ligand; poly(I:C), polyinosinic polycytidylic acid; Tregs, regulatory T cell; FoxP3, forkhead box P3.
This article has been cited by other articles:
|
|
 |
|
  J. Bayry, E. Z. Tchilian, M. N. Davies, E. K. Forbes, S. J. Draper, S. V. Kaveri, A. V. S. Hill, M. D. Kazatchkine, P. C. L. Beverley, D. R. Flower, et al. In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination PNAS, July 22, 2008; 105(29): 10221 - 10226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lacroix-Desmazes, A.-M. Navarrete, S. Andre, J. Bayry, S. V. Kaveri, and S. Dasgupta Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A Blood, July 15, 2008; 112(2): 240 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. George, A. Braun, T. M. Brusko, R. Joseph, S. Bolisetty, C. H. Wasserfall, M. A. Atkinson, A. Agarwal, and M. H. Kapturczak Suppression by CD4+CD25+ Regulatory T Cells Is Dependent on Expression of Heme Oxygenase-1 in Antigen-Presenting Cells Am. J. Pathol., July 1, 2008; 173(1): 154 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Reske, G. Pollara, C. Krummenacher, D. R. Katz, and B. M. Chain Glycoprotein-Dependent and TLR2-Independent Innate Immune Recognition of Herpes Simplex Virus-1 by Dendritic Cells J. Immunol., June 1, 2008; 180(11): 7525 - 7536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ouabed, F.-X. Hubert, D. Chabannes, L. Gautreau, M. Heslan, and R. Josien Differential Control of T Regulatory Cell Proliferation and Suppressive Activity by Mature Plasmacytoid versus Conventional Spleen Dendritic Cells J. Immunol., May 1, 2008; 180(9): 5862 - 5870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Liang, C. Workman, J. Lee, C. Chew, B. M. Dale, L. Colonna, M. Flores, N. Li, E. Schweighoffer, S. Greenberg, et al. Regulatory T Cells Inhibit Dendritic Cells by Lymphocyte Activation Gene-3 Engagement of MHC Class II J. Immunol., May 1, 2008; 180(9): 5916 - 5926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hanig and M. B. Lutz Suppression of Mature Dendritic Cell Function by Regulatory T Cells In Vivo Is Abrogated by CD40 Licensing J. Immunol., February 1, 2008; 180(3): 1405 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Watanabe, P. N. M. Mwinzi, C. L. Black, E. M. O. Muok, D. M. S. Karanja, W. E. Secor, and D. G. Colley T Regulatory Cell Levels Decrease in People Infected With Schistosoma mansoni on Effective Treatment Am J Trop Med Hyg, October 1, 2007; 77(4): 676 - 682. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
