| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Transplantation Research Center, Brigham and Women’s Hospital and Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115;
University of California San Francisco Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0540;
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Acceptance of the fetus expressing allogeneic paternal Ags by the mother is a physiologic model of transplantation tolerance. Various mechanisms contribute to fetal evasion from immune attack by maternal leukocytes. We have recently demonstrated that the inhibitory costimulatory molecule PDL1 plays a critical role in fetomaternal tolerance in that PDL1 blockade or deficiency resulted in decreased allogeneic fetal survival rates. CD4+CD25+ T regulatory cells (Tregs) have also been demonstrated to play an important role in fetomaternal tolerance. Since PDL1 is expressed on Tregs, we explored the interactions between PDL1 and Tregs in vivo in a mouse model of fetomaternal tolerance. Depletion of CD25+ T cells abrogated the effect of anti-PDL1 Ab indicating that the effect of PDL1 is possibly mediated by CD25+ Tregs. Adoptive transfer of Tregs from wild-type but not PDL1-deficient mice into PDL1-deficient recipients significantly improved fetal survival. The frequency, phenotype and placental trafficking of Tregs from PDL1-deficient mice were similar to those of wild-type controls, but were defective in inhibiting alloreactive Th1 cells in vitro. This is the first report providing evidence for a link between PDL1 and T regulatory cells in mediating fetomaternal tolerance.
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 National Institutes of Health Grant R01 AI051559 and P01 AI056299 (to M.H.S.), American Society of Transplantation Basic Scientist Faculty Grant (to I.G.), and National Kidney Foundation Research Fellowship Grant (to A.H.).
2 Address correspondence and reprint requests to Dr. Indira Guleria, Transplantation Research Center, 300 Longwood Avenue, Boston, MA 02115. E-mail address: indira.guleria{at}tch.harvard.edu
3 Abbreviations used in this paper: Treg, regulatory T cell; GITR, glucocorticoid-induced TNFR-related protein; dpc, days post coitum; WT, wild type.
This article has been cited by other articles:
|
|
 |
|
  K. Keeren, M. Friedrich, I. Gebuhr, S. Philipp, R. Sabat, W. Sterry, C. Brandt, C. Meisel, G. Grutz, H.-D. Volk, et al. Expression of Tolerance Associated Gene-1, a Mitochondrial Protein Inhibiting T Cell Activation, Can Be Used to Predict Response to Immune Modulating Therapies J. Immunol., September 15, 2009; 183(6): 4077 - 4087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Guerin, J. R. Prins, and S. A. Robertson Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum. Reprod. Update, September 1, 2009; 15(5): 517 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kool, M. van Nimwegen, M. A. M. Willart, F. Muskens, L. Boon, J. J. Smit, A. Coyle, B. E. Clausen, H. C. Hoogsteden, B. N. Lambrecht, et al. An Anti-Inflammatory Role for Plasmacytoid Dendritic Cells in Allergic Airway Inflammation J. Immunol., July 15, 2009; 183(2): 1074 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wang, K. Pino-Lagos, V. C. de Vries, I. Guleria, M. H. Sayegh, and R. J. Noelle Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells PNAS, July 8, 2008; 105(27): 9331 - 9336. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
