| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Biologie et Thérapeutique des Pathologies Immunitaires, Hôpital Pitié-Salpêtrière, Paris, France;
Diabetes Center, University of California, San Francisco, CA 94143;
Service d’Hématologie Clinique, Hôpital Henri Mondor, Créteil, France; and
Xcyte Therapies, Seattle, WA 98104
CD4+CD25+ immunoregulatory T cells (Tregs) can be administered to inhibit graft-vs-host disease (GVHD) while preserving graft-vs-leukemia activity after allogeneic bone marrow transplantation in mice. Preclinical studies suggest that it is necessary to infuse as many Tregs as conventional donor T cells to achieve a clinical effect on GVHD. Thus, it would be necessary to expand Tregs ex vivo before transplantation. Two strategies have been proposed: expansion of Tregs stimulated by anti-CD3/CD28-coated microbeads for polyclonal activation or by host-type allogeneic APCs for selecting Tregs specific for host Ags. In this study, we describe the mechanisms by which ex vivo-expanded Tregs act on donor T cells to prevent GVHD in mice. We demonstrate that expanded Tregs strongly inhibited the division, expansion, and differentiation of donor T cells, with a more pronounced effect with Tregs specific for host Ags. These latter cells permit the efficient and durable control of GVHD and favor immune reconstitution.
This article has been cited by other articles:
|
|
 |
|
  D. Atanackovic, Y. Cao, T. Luetkens, J. Panse, C. Faltz, J. Arfsten, K. Bartels, C. Wolschke, T. Eiermann, A. R. Zander, et al. CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation Haematologica, March 1, 2008; 93(3): 423 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Ruzek, J. S. Waire, D. Hopkins, G. LaCorcia, J. Sullivan, B. L. Roberts, S. M. Richards, S. R. Nahill, J. M. Williams, A. Scaria, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo Blood, February 1, 2008; 111(3): 1726 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Kish, A. V. Gorbachev, and R. L. Fairchild Regulatory function of CD4+CD25+ T cells from Class II MHC-deficient mice in contact hypersensitivity responses J. Leukoc. Biol., July 1, 2007; 82(1): 85 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Billiard, E. Litvinova, D. Saadoun, F. Djelti, D. Klatzmann, J. L. Cohen, G. Marodon, and B. L. Salomon Regulatory and Effector T Cell Activation Levels Are Prime Determinants of In Vivo Immune Regulation J. Immunol., August 15, 2006; 177(4): 2167 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Nardelli, T. F. Warner, S. M. Callister, and R. F. Schell Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged with Borrelia spp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production. Clin. Vaccine Immunol., August 1, 2006; 13(8): 884 - 891. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
