scholarly journals Post-Transplant Cyclophosphamide (PT/Cy) Preserves Effector (Teff) and Regulatory (Treg) T Cells During Early Immune Reconstitution After Allogeneic Bone Marrow Transplantation

2012 ◽  
Vol 18 (2) ◽  
pp. S224-S225 ◽  
Author(s):  
C.G. Kanakry ◽  
S. Ganguly ◽  
F.J. Bolanos Meade ◽  
M.L. Zahurak ◽  
F. Kos ◽  
...  
2000 ◽  
Vol 69 (7) ◽  
pp. 1341-1347 ◽  
Author(s):  
Glenda M. Davison ◽  
Nicolas Novitzky ◽  
Almaree Kline ◽  
Valda Thomas ◽  
Louise Abrahams ◽  
...  

Blood ◽  
2018 ◽  
Vol 132 (22) ◽  
pp. 2351-2361 ◽  
Author(s):  
Lauren P. McLaughlin ◽  
Rayne Rouce ◽  
Stephen Gottschalk ◽  
Vicky Torrano ◽  
George Carrum ◽  
...  

Abstract There is a Blood Commentary on this article in this issue.


Cytotherapy ◽  
2014 ◽  
Vol 16 (7) ◽  
pp. 976-989 ◽  
Author(s):  
Miriam Perlingeiro Beltrame ◽  
Mariester Malvezzi ◽  
Carmem Bonfim ◽  
Dimas Tadeu Covas ◽  
Alberto Orfao ◽  
...  

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 873-885 ◽  
Author(s):  
Margot Zöller ◽  
Annette Schmidt ◽  
Angela Denzel ◽  
Jürgen Moll

Abstract Constitutive expression of a rat CD44 variant isoform, rCD44v4-v7, on murine T cells accelerates immune responsiveness. Because prolonged immunodeficiency can be a major drawback in allogeneic bone marrow transplantation, we considered it of special interest to see whether repopulation of lethally irradiated syngeneic and allogeneic mice may be influenced by constitutive expression of the rCD44v4-v7 transgene. When lethally irradiated syngeneic and allogeneic mice were reconstituted with bone marrow cells (BMC) from rCD44v4-v7 transgenic (TG) or nontransgenic (NTG) mice, the former had a clear repopulation advantage: thymocytes expanded earlier after reconstitution and, as a consequence, higher numbers of lymphocytes were recovered from spleen and lymph nodes. Lymphocytes also displayed functional activity in advance to those from mice reconstituted with BMC from NTG mice. Most importantly, after the transfer of BMC from TG mice into an allogeneic host, the frequency of host-reactive T cells decreased rapidly. Apparently, this was due to accelerated induction of tolerance. Because these effects were counterregulated by an rCD44v6-specific antibody, it is likely that they could be attributed to the rCD44v4-v7 TG product. Thus, expression of a CD44 variant isoform at high levels facilitated reconstitution with allogeneic BMC by accelerated establishment of tolerance and the regaining of immunocompetence.


Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4358-4369 ◽  
Author(s):  
Barbara C. Godthelp ◽  
Maarten J.D. van Tol ◽  
Jaak M. Vossen ◽  
Peter J. van den Elsen

To evaluate the role of T-cell selection in the thymus and/or periphery in T-cell immune reconstitution after allogeneic bone marrow transplantation (allo-BMT), we have analyzed the overall and antigen-specific T-cell repertoires in pediatric allo-BMT recipients treated for leukemia. We observed a lack of overall T-cell receptor (TCR) diversity in the repopulating T cells at 3 months after allo-BMT, as was deduced from complementarity determining region 3 (CDR3) size distribution patterns displaying reduced complexity. This was noted particularly in recipients of a T-cell–depleted (TCD) graft and, to a lesser extent, also in recipients of unmanipulated grafts. At 1 year after allo-BMT, normalization was observed of TCR CDR3 size complexity in almost all recipients. Analysis of the antigen-specific T-cell repertoire at 1 year after BMT showed that the T cells responding to tetanus toxoid (TT) differed in TCR gene segment usage and in amino acid composition of the CDR3 region when comparing the recipient with the donor. Moreover, the TT-specific TCR repertoire was found to be stable within a given allo-BMT recipient, because TT-specific T cells with completely identical TCRs were found at 3 consecutive years after transplantation. These observations suggest an important role for T-cell selection processes in the complete restoration of the T-cell immune repertoire in children after allo-BMT.


Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 4080-4088 ◽  
Author(s):  
Mathias M. Hauri-Hohl ◽  
Marcel P. Keller ◽  
Jason Gill ◽  
Katrin Hafen ◽  
Esther Pachlatko ◽  
...  

Abstract Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor T cells secrete IFN-γ, which in turn stimulates the programmed cell death of thymic epithelial cells (TECs). Because TECs themselves are competent and sufficient to prime naive allospecific T cells and to elicit their effector function, the elimination of host-type professional antigen-presenting cells (APCs) does not prevent donor T-cell activation and TEC apoptosis, thus precluding normal thymopoiesis in transplant recipients. Hence, strategies that protect TECs may be necessary to improve immune reconstitution following allogeneic bone marrow transplantation.


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