| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Service de Recherches en Hémato-Immunologie, Commissariat à l’Energie Atomique -Direction des Sciences du Vivant, Département de Recherche Médicale, Hôpital Saint-Louis, Institut Universitaire d’Hématologie, Paris, France;
Département de Néphrologie et Transplantation, Hôpital du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France; and
Département d’Anatomo-Pathologie, Hôpital Paul Brousse, Villejuif, France
The soluble HLA-G5 isoform encoded by intron-4 retaining spliced transcript has been previously detected in vivo in sera and grafts from transplanted patients who had significantly better graft acceptance. These findings led us to investigate the role of HLA-G5 in tolerance induction in vitro and its biological relevance in allograft acceptance in vivo. We demonstrated that engagement of Ig-like transcript-2 and Ig-like transcript-4 receptors by HLA-G5 is involved in inhibition of T cell alloproliferative responses. Naive T cells sensitized in vitro with HLA-G5, for as little as 18 h, 1) lost their ability to respond to subsequent allogeneic stimulus, and 2) acquired regulatory properties because they inhibited the reactivity of other T cells. These HLA-G5-induced T cells act in an Ag-nonspecific fashion and through soluble factors. Biological relevance was provided by ex vivo analyzes of samples from liver-kidney cotransplanted patients who had high HLA-G5 serum levels and no graft rejection. We showed that addition of HLA-G5-containing sera from these patients inhibited T cell alloresponses and that serum HLA-G5 was responsible for this inhibition. Notably, PBMC from transplanted patients exposed to high levels of circulating HLA-G5 did not respond to allostimulation and inhibited alloreactivity of other T cells. These results demonstrate that HLA-G5-mediated tolerance involves the induction of immunosuppressive T cells. These findings provide evidence supporting the tolerogenic properties of HLA-G and emphasize its potential application as a relevant therapeutic candidate capable of limiting allograft rejection.
This article has been cited by other articles:
|
|
 |
|
  R. Bahri, A. Naji, C. Menier, B. Charpentier, E. D. Carosella, N. Rouas-Freiss, and A. Durrbach Dendritic Cells Secrete the Immunosuppressive HLA-G Molecule upon CTLA4-Ig Treatment: Implication in Human Renal Transplant Acceptance J. Immunol., December 1, 2009; 183(11): 7054 - 7062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Botturi, Y. Lacoeuille, P. Thomas, S. Boniface, M. Reynaud-Gaubert, and A. Magnan CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients Eur. Respir. J., June 1, 2008; 31(6): 1167 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Carosella, B. Favier, N. Rouas-Freiss, P. Moreau, and J. LeMaoult Beyond the increasing complexity of the immunomodulatory HLA-G molecule Blood, May 15, 2008; 111(10): 4862 - 4870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fainardi, R. Rizzo, L. Melchiorri, M. Stignani, M. Castellazzi, C. Tamborino, E. Paolino, M. Tola, E. Granieri, and O. Baricordi CSF levels of soluble HLA-G and Fas molecules are inversely associated to MRI evidence of disease activity in patients with relapsing--remitting multiple sclerosis Multiple Sclerosis, May 1, 2008; 14(4): 446 - 454. [Abstract] [PDF]
|
|
|
|
|
|
A. Naji, S. Le Rond, A. Durrbach, I. Krawice-Radanne, C. Creput, M. Daouya, J. Caumartin, J. LeMaoult, E. D. Carosella, and N. Rouas-Freiss CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance Blood, December 1, 2007; 110(12): 3936 - 3948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Guleria and M. H. Sayegh Maternal Acceptance of the Fetus: True Human Tolerance J. Immunol., March 15, 2007; 178(6): 3345 - 3351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. LeMaoult, J. Caumartin, M. Daouya, B. Favier, S. L. Rond, A. Gonzalez, and E. D. Carosella Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells Blood, March 1, 2007; 109(5): 2040 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. van der Meer, H.G.M. Lukassen, B. van Cranenbroek, E.H. Weiss, D.D.M. Braat, M.J. van Lierop, and I. Joosten Soluble HLA-G promotes Th1-type cytokine production by cytokine-activated uterine and peripheral natural killer cells Mol. Hum. Reprod., February 1, 2007; 13(2): 123 - 133. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
