scholarly journals Treatment of Donors with Death Receptor 3 Agonistic Fusion Protein TL1A-Ig (with and Without Low Dose IL-2) Leads to Regulatory T Cell Expansion and Activation with Reduction in Graft-Versus-Host Disease

2018 ◽  
Vol 24 (3) ◽  
pp. S191-S192
Author(s):  
Melissa Mavers ◽  
Kristina Maas-Bauer ◽  
Hidekazu Nishikii ◽  
Federico Simonetta ◽  
Maite Alvarez ◽  
...  
Keyword(s):  
T Cell ◽  
Fusion Protein ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Cell Expansion ◽  
Low Dose ◽  
Death Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Death Receptor 3

191 Interleukin 4 Is Critical in Helminth-Induced Regulatory T-Cell Expansion and Suppression of Colitis in a Graft Versus Host Disease Model

2016 ◽  
Vol 150 (4) ◽  
pp. S50
Author(s):  
Yue Li ◽  
Hung-Lin Chen ◽  
George J. Weiner ◽  
Richard S. Blumberg ◽  
Bruce R. Blazar ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Cell Expansion ◽  
Disease Model ◽  
Interleukin 4 ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Expansion

scholarly journals Low-Dose Interleukin-2 Therapy Restores Regulatory T Cell Homeostasis in Patients with Chronic Graft-Versus-Host Disease

2013 ◽  
Vol 5 (179) ◽  
pp. 179ra43-179ra43 ◽  
Author(s):  
K.-i. Matsuoka ◽  
J. Koreth ◽  
H. T. Kim ◽  
G. Bascug ◽  
S. McDonough ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Low Dose ◽  
Interleukin 2 ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Activation of the DR3-TL1A Axis in Donor Mice Leads to Regulatory T Cell Expansion and Activation With Reduction in Graft-Versus-Host Disease

2019 ◽  
Vol 10 ◽  
Author(s):  
Melissa Mavers ◽  
Federico Simonetta ◽  
Hidekazu Nishikii ◽  
Jessica V. Ribado ◽  
Kristina Maas-Bauer ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Cell Expansion ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Expansion

scholarly journals A Crucial Role for Host APCs in the Induction of Donor CD4+CD25+ Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease

2010 ◽  
Vol 185 (7) ◽  
pp. 3866-3872 ◽  
Author(s):  
Isao Tawara ◽  
Warren D. Shlomchik ◽  
Angela Jones ◽  
Weiping Zou ◽  
Evelyn Nieves ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Crucial Role ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Graft-versus-host disease reduces regulatory T-cell migration into the tumour tissue

Immunology ◽  
2012 ◽  
Vol 137 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Christoph Dürr ◽  
Marie Follo ◽  
Marco Idzko ◽  
Wilfried Reichardt ◽  
Robert Zeiser
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Tumour Tissue ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Migration

scholarly journals Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5502-5510 ◽  
Author(s):  
Jack Gorski ◽  
Xiao Chen ◽  
Mariya Gendelman ◽  
Maryam Yassai ◽  
Ashley Krueger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Expansion ◽  
Host Disease ◽  
Host Environment ◽  
Graft Versus Host ◽  
T Cell Reconstitution ◽  
T Cell Expansion ◽  
Cell Defect

Abstract Graft versus host disease (GVHD) typically results in impaired T-cell reconstitution characterized by lymphopenia and repertoire skewing. One of the major causes of inadequate T-cell reconstitution is that T-cell survival and expansion in the periphery are impaired. In this report, we have performed adoptive transfer studies to determine whether the quantitative reduction in T-cell numbers is due to an intrinsic T-cell defect or whether the environmental milieu deleteriously affects T-cell expansion. These studies demonstrate that T cells obtained from animals with graft-versus-host disease (GVHD) are capable of significant expansion and renormalization of an inverted CD4/CD8 ratio when they are removed from this environment. Moreover, these cells can generate complex T-cell repertoires early after transplantation and are functionally competent to respond to third-party alloantigens. Our data indicate that T cells from mice undergoing GVHD can respond to homeostatic signals in the periphery and are not intrinsically compromised once they are removed from the GVHD environment. We thereby conclude that the host environment and not an intrinsic T-cell defect is primarily responsible for the lack of effective T-cell expansion and diversification of complex T-cell repertoires that occurs during GVHD.

scholarly journals Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease

2019 ◽  
Vol 3 (7) ◽  
pp. 984-994 ◽  
Author(s):  
Jennifer S. Whangbo ◽  
Haesook T. Kim ◽  
Sarah Nikiforow ◽  
John Koreth ◽  
Ana C. Alho ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Low Dose ◽  
B Cell Lymphoma ◽  
Host Disease ◽  
Graft Versus Host ◽  
Response Groups

Abstract Patients with chronic graft-versus-host disease (cGVHD) have a paucity of regulatory CD4 T cells (CD4Tregs) that mediate peripheral tolerance. In clinical trials, daily low-dose interleukin-2 (IL-2) has been administered safely for prolonged periods in patients with steroid-refractory cGVHD. Peripheral CD4Tregs expand dramatically in all patients during IL-2 therapy but clinical improvement was observed in ∼50% of patients. Here, we examined the impact of low-dose IL-2 therapy on functional T-cell markers and the T-cell repertoire within CD4Tregs, conventional CD4 T cells (CD4Tcons), and CD8+ T cells. IL-2 had profound effects on CD4Tregs homeostasis in both response groups including selective expansion of the naive subset, improved thymic output, and increased expression of Ki67, FOXP3, and B-cell lymphoma 2 within CD4Tregs. Similar changes were not seen in CD4Tcons or CD8 T cells. Functionally, low-dose IL-2 enhanced, in vitro, CD4Treg-suppressive activity in both response groups, and all patient CD4Tcons were similarly suppressed by healthy donor CD4Tregs. High-throughput sequencing of the T-cell receptor β (TCRβ) locus demonstrated that low-dose IL-2 therapy increased TCR repertoire diversity and decreased evenness within CD4Tregs without affecting CD4Tcons or CD8 T cells. Using clone-tracking analysis, we observed rapid turnover of highly prevalent clones in CD4Tregs as well as the conversion of CD4Tcons to CD4Tregs. After 12 weeks of daily IL-2, clinical responders had a greater influx of novel clones within the CD4Treg compartment compared with nonresponders. Further studies to define the function and specificity of these novel CD4Treg clones may help establish the mechanisms whereby low-dose IL-2 therapy promotes immune tolerance.

scholarly journals Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0124927 ◽  
Author(s):  
Sarvari Velaga ◽  
Sya N. Ukena ◽  
Ulrike Dringenberg ◽  
Christina Alter ◽  
Julian Pardo ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Granzyme A

scholarly journals Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host disease without global immunosuppression

2010 ◽  
Vol 207 (12) ◽  
pp. 2551-2559 ◽  
Author(s):  
Jörn C. Albring ◽  
Michelle M. Sandau ◽  
Aaron S. Rapaport ◽  
Brian T. Edelson ◽  
Ansuman Satpathy ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Lymphocyte ◽  
Graft Versus Host Disease ◽  
Cell Expansion ◽  
Tumor Necrosis Factor Receptor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Life Threatening

Graft-versus-host disease (GVHD) causes significant morbidity and mortality in allogeneic hematopoietic stem cell transplantation (aHSCT), preventing its broader application to non–life-threatening diseases. We show that a single administration of a nondepleting monoclonal antibody specific for the coinhibitory immunoglobulin receptor, B and T lymphocyte associated (BTLA), permanently prevented GVHD when administered at the time of aHSCT. Once GVHD was established, anti-BTLA treatment was unable to reverse disease, suggesting that its mechanism occurs early after aHSCT. Anti-BTLA treatment prevented GVHD independently of its ligand, the costimulatory tumor necrosis factor receptor herpesvirus entry mediator (HVEM), and required BTLA expression by donor-derived T cells. Furthermore, anti-BTLA treatment led to the relative inhibition of CD4+ forkhead box P3− (Foxp3−) effector T cell (T eff cell) expansion compared with precommitted naturally occurring donor-derived CD4+ Foxp3+ regulatory T cell (T reg cell) and allowed for graft-versus-tumor (GVT) effects as well as robust responses to pathogens. These results suggest that BTLA agonism rebalances T cell expansion in lymphopenic hosts after aHSCT, thereby preventing GVHD without global immunosuppression. Thus, targeting BTLA with a monoclonal antibody at the initiation of aHSCT therapy might reduce limitations imposed by histocompatibility and allow broader application to treatment of non–life-threatening diseases.

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