scholarly journals Regulatory Immunotherapy in Bone Marrow Transplantation

2011 ◽  
Vol 11 ◽  
pp. 2620-2634
Author(s):  
Vanessa Morales-Tirado ◽  
Wioleta Luszczek ◽  
Marié van der Merwe ◽  
Asha Pillai
Keyword(s):  
T Cells ◽  
Tolerance Induction ◽  
Donor Cell ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Conditioning Treatment ◽  
Donor Type ◽  
Nonmalignant Disease ◽  
Immunoregulatory T Cells ◽  
Killer T Cells

Every year individuals receive hematopoietic stem cell transplantation (HSCT) to eradicate malignant and nonmalignant disease. The immunobiology of allotransplantation is an area of ongoing discovery, from the recipient's conditioning treatment prior to the transplant to the donor cell populations responsible for engraftment, graft-versus-host disease, and graft-versus-tumor effect. In this review, we focus on donor-type immunoregulatory T cells, namely, natural killer T cells (NKT) and regulatory T cells (Treg), and their current and potential roles in tolerance induction after allogeneic HSCT.

scholarly journals CD4+CD25+ Immunoregulatory T Cells

2002 ◽  
Vol 196 (3) ◽  
pp. 401-406 ◽  
Author(s):  
José L. Cohen ◽  
Aurélie Trenado ◽  
Douglas Vasey ◽  
David Klatzmann ◽  
Benoît L. Salomon
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Ex Vivo ◽  
Tolerance Induction ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Type Antigen ◽  
Organ Specific ◽  
Antigen Presenting ◽  
Immunoregulatory T Cells

CD4+CD25+ immunoregulatory T cells play a pivotal role in preventing organ-specific autoimmune diseases and in tolerance induction to allogeneic organ transplants. We investigated whether these cells could also control graft-versus-host disease (GVHD), the main complication after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we show that the few CD4+CD25+ T cells naturally present in the transplant regulate GVHD because their removal from the graft dramatically accelerates this disease. Furthermore, the addition of freshly isolated CD4+CD25+ T cells at time of grafting significantly delays or even prevents GVHD. Ex vivo–expanded CD4+CD25+ regulatory T cells obtained after stimulation by allogeneic recipient-type antigen-presenting cells can also modulate GVHD. Thus, CD4+CD25+ regulatory T cells represent a new therapeutic tool for controlling GVHD in allogeneic HSCT. More generally, these results outline the tremendous potential of regulatory T cells as therapeutics.

scholarly journals Reduced dose of PTCy followed by adjuvant α-galactosylceramide enhances GVL effect without sacrificing GVHD suppression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Makoto Nakamura ◽  
Yusuke Meguri ◽  
Shuntaro Ikegawa ◽  
Takumi Kondo ◽  
Yuichi Sumii ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell Subsets ◽  
Inkt Cells ◽  
Early Recovery ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Reduced Dose ◽  
Graft Versus Leukemia ◽  
Novel Strategy

AbstractPosttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient’s condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by α-galactosylceramide (α-GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of α-GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4+Foxp3+ regulatory T cells. These studies indicate that α-GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.

Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Vα14 natural killer T cells

2006 ◽  
Vol 106 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Masaki Kuwatani ◽  
Yoshinori Ikarashi ◽  
Akira Iizuka ◽  
Chihiro Kawakami ◽  
Gary Quinn ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Graft Versus Host Disease ◽  
Adoptive Transfer ◽  
Natural Killer T Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Killer T Cells ◽  
Acute Graft

Depletion of alloreactive T cells for tolerance induction in a recipient of kidney and hematopoietic stem cell transplantations

2012 ◽  
Vol 16 (8) ◽  
pp. E342-E347
Author(s):  
Kanchana Tangnararatchakit ◽  
Wiwat Tirapanich ◽  
Usanarat Anurathapan ◽  
Wiwat Tapaneya-Olarn ◽  
Samart Pakakasama ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Tolerance Induction ◽  
Hematopoietic Stem ◽  
Alloreactive T Cells
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