scholarly journals Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance

2017 ◽  
Vol 17 (8) ◽  
pp. 2020-2032 ◽  
Author(s):  
B. Sprangers ◽  
S. DeWolf ◽  
T. M. Savage ◽  
T. Morokata ◽  
A. Obradovic ◽  
...  
Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5898-5908 ◽  
Author(s):  
Renee J. Robb ◽  
Katie E. Lineburg ◽  
Rachel D. Kuns ◽  
Yana A. Wilson ◽  
Neil C. Raffelt ◽  
...  

Abstract FoxP3+ confers suppressive properties and is confined to regulatory T cells (Treg) that potently inhibit autoreactive immune responses. In the transplant setting, natural CD4+ Treg are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8+ population of FoxP3+ Treg that convert from CD8+ conventional donor T cells after allogeneic but not syngeneic bone marrow transplantation. These CD8+ Treg undergo conversion in the mesenteric lymph nodes under the influence of recipient dendritic cells and TGF-β. Importantly, this population is as important for protection from GVHD as the well-studied natural CD4+FoxP3+ population and is more potent in exerting class I–restricted and antigen-specific suppression in vitro and in vivo. Critically, CD8+FoxP3+ Treg are exquisitely sensitive to inhibition by cyclosporine but can be massively and specifically expanded in vivo to prevent GVHD by coadministering rapamycin and IL-2 antibody complexes. CD8+FoxP3+ Treg thus represent a new regulatory population with considerable potential to preferentially subvert MHC class I–restricted T-cell responses after bone marrow transplantation.


10.1038/nm915 ◽  
2003 ◽  
Vol 9 (9) ◽  
pp. 1144-1150 ◽  
Author(s):  
Matthias Edinger ◽  
Petra Hoffmann ◽  
Joerg Ermann ◽  
Kathryn Drago ◽  
C Garrison Fathman ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document