scholarly journals Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice

Blood ◽  
2013 ◽  
Vol 121 (22) ◽  
pp. 4595-4602 ◽  
Author(s):  
Amar Nijagal ◽  
Chris Derderian ◽  
Tom Le ◽  
Erin Jarvis ◽  
Linda Nguyen ◽  
...  

Key Points Tolerance induction after in utero hematopoietic cell transplantation involves both direct and indirect antigen presentation. Tolerance is achieved by deletion of effector T cells, which results in Treg enrichment without de novo Treg induction.

2018 ◽  
Vol 2 (6) ◽  
pp. 681-690 ◽  
Author(s):  
Lori Muffly ◽  
Kevin Sheehan ◽  
Randall Armstrong ◽  
Kent Jensen ◽  
Keri Tate ◽  
...  

Key Points Phenotypic TM isolation from unmanipulated donor apheresis via CD45RA depletion followed by CD8+ enrichment is feasible. TM infusion for patients with relapse after allogeneic HCT was safe and resulted in minimal GVHD.


2009 ◽  
Vol 209 (3) ◽  
pp. S84
Author(s):  
Demetri J. Merianos ◽  
Eleonor Tiblad ◽  
Matthew T. Santore ◽  
Carlyn A. Todorow ◽  
Philip W. Zoltick ◽  
...  

2020 ◽  
Vol 4 (6) ◽  
pp. 1102-1114
Author(s):  
John S. Riley ◽  
Lauren E. McClain ◽  
John D. Stratigis ◽  
Barbara E. Coons ◽  
Nicholas J. Ahn ◽  
...  

Abstract In utero hematopoietic cell transplantation (IUHCT) has the potential to cure congenital hematologic disorders including sickle cell disease. However, the window of opportunity for IUHCT closes with the acquisition of T-cell immunity, beginning at approximately 14 weeks gestation, posing significant technical challenges and excluding from treatment fetuses evaluated after the first trimester. Here we report that regulatory T cells can promote alloengraftment and preserve allograft tolerance after the acquisition of T-cell immunity in a mouse model of late-gestation IUHCT. We show that allografts enriched with regulatory T cells harvested from either IUHCT-tolerant or naive mice engraft at 20 days post coitum (DPC) with equal frequency to unenriched allografts transplanted at 14 DPC. Long-term, multilineage donor cell chimerism was achieved in the absence of graft-versus-host disease or mortality. Decreased alloreactivity among recipient T cells was observed consistent with donor-specific tolerance. These findings suggest that donor graft enrichment with regulatory T cells could be used to successfully perform IUHCT later in gestation.


2011 ◽  
Vol 121 (2) ◽  
pp. 582-592 ◽  
Author(s):  
Amar Nijagal ◽  
Marta Wegorzewska ◽  
Erin Jarvis ◽  
Tom Le ◽  
Qizhi Tang ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (6) ◽  
pp. 973-980 ◽  
Author(s):  
S. Christopher Derderian ◽  
P. Priya Togarrati ◽  
Charmin King ◽  
Patriss W. Moradi ◽  
Damien Reynaud ◽  
...  

Key Points In utero injection of an antibody against the c-Kit receptor can effectively deplete host HSCs in mice. In utero depletion of host HSCs leads to significantly increased engraftment after neonatal congenic hematopoietic cell transplantation.


2019 ◽  
Vol 3 (21) ◽  
pp. 3419-3431
Author(s):  
Bettina P. Iliopoulou ◽  
Katie Hsu ◽  
Magdiel Pérez-Cruz ◽  
Sai-Wen Tang ◽  
Wendy W. Pang ◽  
...  

Key Points Administration of anti–TIM-1 blocking mAb ameliorates acute GVHD while preserving graft-versus-tumor effects. Treatment with anti–TIM-1 blocking mAb does not affect proliferation of donor allogeneic T cells.


2018 ◽  
Vol 201 (5) ◽  
pp. 1549-1557 ◽  
Author(s):  
John S. Riley ◽  
Lauren E. McClain ◽  
John D. Stratigis ◽  
Barbara E. Coons ◽  
Haiying Li ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1974 ◽  
Author(s):  
Linde Dekker ◽  
Coco de Koning ◽  
Caroline Lindemans ◽  
Stefan Nierkens

Allogeneic (allo) hematopoietic cell transplantation (HCT) is the only curative treatment option for patients suffering from chemotherapy-refractory or relapsed hematological malignancies. The occurrence of morbidity and mortality after allo-HCT is still high. This is partly correlated with the immunological recovery of the T cell subsets, of which the dynamics and relations to complications are still poorly understood. Detailed information on T cell subset recovery is crucial to provide tools for better prediction and modulation of adverse events. Here, we review the current knowledge regarding CD4+ and CD8+ T cells, γδ T cells, iNKT cells, Treg cells, MAIT cells and naive and memory T cell reconstitution, as well as their relations to outcome, considering different cell sources and immunosuppressive therapies. We conclude that the T cell subsets reconstitute in different ways and are associated with distinct adverse and beneficial events; however, adequate reconstitution of all the subsets is associated with better overall survival. Although the exact mechanisms involved in the reconstitution of each T cell subset and their associations with allo-HCT outcome need to be further elucidated, the data and suggestions presented here point towards the development of individualized approaches to improve their reconstitution. This includes the modulation of immunotherapeutic interventions based on more detailed immune monitoring, aiming to improve overall survival changes.


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