scholarly journals Paradoxical Regulation of Allogeneic Bone Marrow Engraftment and Immune Privilege by Mesenchymal Cells and Adenosine

Author(s):  
Miwako Kakiuchi ◽  
Yuichi Hirata ◽  
Simon C. Robson ◽  
Joji Fujisaki
Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1166-1172 ◽  
Author(s):  
Boris Nikolic ◽  
Guiling Zhao ◽  
Kirsten Swenson ◽  
Megan Sykes

The treatment of mice with anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) on day −5, plus 3 Gy whole body irradiation (WBI) and 7 Gy thymic irradiation (TI) on day 0, allows fully major-histocompatibility-complex–mismatched allogeneic bone marrow engraftment and the induction of immunologic tolerance. TI is required in this model to overcome alloreactivity and possibly to make “space” in the recipient thymus so that lasting central tolerance can be achieved. In addition to suppressing mature T cells in the periphery, Cyclosporine A (CYA) and glucocorticoids have a powerful influence on the thymus. In this study, we evaluated whether the administration of CYA to recipient mice for 12 days prior to bone marrow transplant (BMT), of glucocorticosteroids on the day of BMT, or a combination of both, could create space and overcome alloresistance in the thymus by specifically depleting immature and mature thymocytes prior to BMT. High levels of multilineage donor hematopoietic repopulation and specific transplantation tolerance were achieved in mice treated from days −15 to −3 with CYA (20 mg/kg/d subcutaneously), anti-CD4/CD8 mAbs on day −5, followed by 3 Gy WBI and 15 × 106 allogeneic bone marrow cells on day 0. Vβ analysis suggested a central deletional tolerance mechanism. The same treatment without CYA pretreatment allowed only transient chimerism, without tolerance. Corticosteroid treatment abolished the engraftment-promoting and tolerance-inducing effects of CYA. These results demonstrate a novel pretransplantation-only application of CYA, which facilitates allogeneic marrow engraftment with minimal conditioning, by creating thymic space and/or overcoming intrathymic alloresistance.


Blood ◽  
1967 ◽  
Vol 30 (6) ◽  
pp. 805-811 ◽  
Author(s):  
R. STORB ◽  
R. B. EPSTEIN ◽  
H. RAGDE ◽  
J. BRYANT ◽  
E. D. THOMAS

Abstract Infusion of white blood cells separated from peripheral blood produced allogeneic bone marrow engraftment in lethally irradiated dogs. Approximately 100 x 109 leukocytes obtained from a single donor over an 8-day period were adequate to establish marrow repopulation. Marrow engraftment was indicated by rising blood count, marrow histology, and, in one instance, cytogenetic studies. Marrow grafts were associated with a severe secondary syndrome. Survival was prolonged with methotrexate.


2013 ◽  
Vol 65 (8) ◽  
pp. 585-596 ◽  
Author(s):  
Yuanyuan Wang ◽  
Xinjian Chen ◽  
Schickwann Tsai ◽  
Alun Thomas ◽  
Judith A. Shizuru ◽  
...  

1998 ◽  
Vol 21 (4) ◽  
pp. 327-330 ◽  
Author(s):  
JD Down ◽  
GR Westerhof ◽  
A Boudewijn ◽  
R Setroikromo ◽  
RE Ploemacher

2008 ◽  
Vol 41 (11) ◽  
pp. 927-934 ◽  
Author(s):  
J S Thompson ◽  
R Asmis ◽  
Y Chu ◽  
J Glass ◽  
B Nelson ◽  
...  

Blood ◽  
2016 ◽  
Vol 127 (9) ◽  
pp. 1202-1205 ◽  
Author(s):  
Maite Alvarez ◽  
Kai Sun ◽  
William J. Murphy

Key Points Unlicensed NK cells release GM-CSF upon allogeneic MHCI recognition, which promotes donor allogeneic BMC engraftment.


2009 ◽  
Vol 182 (12) ◽  
pp. 7364-7369 ◽  
Author(s):  
Marieke Bruinsma ◽  
Peter L. van Soest ◽  
Pieter J. M. Leenen ◽  
Bob Löwenberg ◽  
Jan J. Cornelissen ◽  
...  

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