scholarly journals IL-7 Is the Limiting Homeostatic Factor that Constrains Homeostatic Proliferation of CD8+ T Cells after Allogeneic Stem Cell Transplantation and Graft-versus-Host Disease

2019 ◽  
Vol 25 (4) ◽  
pp. 648-655 ◽  
Author(s):  
Simon-David Gauthier ◽  
Moutuaata M. Moutuou ◽  
Francis Daudelin ◽  
Dominique Leboeuf ◽  
Martin Guimond
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Homeostatic Proliferation ◽  
Host Disease ◽  
Graft Versus Host

Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation

Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3745-3758 ◽  
Author(s):  
Emily Blyth ◽  
Leighton Clancy ◽  
Renee Simms ◽  
Chun K. K. Ma ◽  
Jane Burgess ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Organ Damage ◽  
Host Disease ◽  
Graft Versus Host ◽  
Key Points

Key Points Infusion of CMV-specific T cells early posttransplant does not increase acute or chronic graft-versus-host disease. CMV-specific T cells early posttransplant reduce the need for pharmacotherapy without increased rates of CMV-related organ damage.

A Pilot Study of Mycophenolate Mofetil for the Prophylaxis and Treatment of Graft-Versus-Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4969-4969
Author(s):  
Chengwei Luo ◽  
Xin Du ◽  
Jianyu Weng ◽  
Rong Guo ◽  
Zesheng Lu
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Peripheral Blood Stem Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

Abstract Graft-versus-host disease (GVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT), which contribute to morbidity and mortality after transplantation. Approximately half of the patients that undergo allogeneic stem cell transplantation develop severe acute or chronic graft-versus-host disease [Shulman HM et al. Am J Med, 1980], which varies with the degree of histoincompatibility, the recipient and donor ages, the source and quality of donor T lymphocytes, the incidence of cytomegalovirus infection,and type of GVHD prophylaxis strategy. The combination of immunosuppressive drugs, CsA and short-course MTX is a standard regiment for prevention of GVHD after BMT [Nademanee A et al. Blood, 1995], and have been shown in randomize trials to be superior to either drug alone in preventing severe GVHD [Storb R N Engl J Med.1986]. Although the efficacy of the regimens in preventing GVHD, the incidence reported for GVHD after transplantation is 38–68%. Each of these agents is also associated with significant organ toxicity. MMF is an new immunosuppressive drug, which selectively inhibits proliferation of T and B lymphocytes, formation of antibodies, and glycosylation of adhesion molecules by inhibition purine nucleotide synthesis and depleting the lymphocytes and monocytes of guanosine triphosphate. In patients undergoing renal and heart transplantation, it has been successfully used to prevent graft rejection [Lang P et al.Transplantation, 2005]. We compared the effects of MMF+ CsA+ MTX as GVHD prophylaxis vs CsA + MTX in patients undergoing allogeneic peripheral blood stem cell transplantation. In all, 33 patients were enrolled in this study. The first group, of 16 patients, received CsA at 3mg/kg i.v. from day −1 to +30 day and MTX was on 15mg/m2 day +1 and 10mg/m2 day +3, +6, +11. The other group, of 17 patients received MMF 1g/d day −7 until day 0 and CsA + MTX. Here we used flow cytometric analysis technique to measure the changes of T cell subsets before and after treatment of MMF and CsA. Our study showed the incident of aGVHD is 25% when we combined standard GVHD proplylaxis with MMF after PBSCT, Which significantly reduce the risk of aGVHD than the combination of CsA and MTX (58.8%). Therefore, MMF is an effective drug in prophylaxis of aGVHD. Chronic GVHD is a late complication of PBSCT, Which develops approximately 30% in related donor HLA-matched allografts, and 60–70% in HLA-unmatched. The incident is not reduce with the development of aGVHD prophylaxis, Our result showed that the incident of cGVHD in research group (25%) is the same as the control group (23.5%). It seems that MMF is not reduce the incident of cGVHD, which may be different frome aGVHD. Our conclude that the number of CD3+ CD4+T cells decreased after the treatment of MMF, and those of CD3+ CD8+T cells increased,with reduction of the CD4+/CD8+ ratio. the number of CD25+ CD4+ and CD69+ CD8+ T cells were all increase. It seems that MMF may preferably effect on the CD3+CD4+T cells and the combination of MMF with CSA and MTX can significantly reduce the incidence of acute graft-vost-host diease, It appears to have a synergic action with CSA for the treatment of aGVHD.

scholarly journals Decreased Levels of Circulating IL17-Producing CD161+CCR6+ T Cells Are Associated with Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e50896 ◽  
Author(s):  
Anniek B. van der Waart ◽  
Walter J. F. M. van der Velden ◽  
Astrid G. S. van Halteren ◽  
Marij J. L. G. Leenders ◽  
Ton Feuth ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Host Disease ◽  
Graft Versus Host

CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3827-3832 ◽  
Author(s):  
Karen P. Piper ◽  
Claire Horlock ◽  
S. John Curnow ◽  
Julie Arrazi ◽  
Sarah Nicholls ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Anatomic Site ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Acute graft-versus-host disease (aGVHD) remains a serious complication following allogeneic stem-cell transplantation (SCT), and is mediated by infiltration of alloreactive donor T cells into recipient tissue. Chemokines and their receptors play a central role in controlling the recruitment of T cells into discrete tissue sites, and determine the clinical features of GVHD in murine models. In this study, we have analyzed the serum concentration of molecules that control leukocyte migration in serial samples from 34 patients following allogeneic SCT. The chemokine CXCL10 (IP-10) was significantly elevated (> 2-fold) in serum at the time of aGVHD. Because the ligand for CXCL10 is CXCR3, the number of CXCR3+ T cells was determined in peripheral blood, but was not increased during episodes of GVHD. To investigate the role of chemokines in the recruitment of T cells to the anatomic site of GVHD, skin biopsies were stained for CXCL10 and CXCR3 expression. CXCL10 expression was observed in the basal keratinocytes of the epidermis in patients with GVHD together with positive staining for CXCR3 on cells in dermal infiltrates. These findings indicate that CXCL10 plays a central role in the pathogenesis of skin aGVHD by the recruitment of CXCR3+ T cells to the sites of inflammation.

scholarly journals Interleukin-10 Gene-Modified Dendritic Cell-Induced Type 1 Regulatory T Cells Induce Transplant-Tolerance and Impede Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

2017 ◽  
Vol 43 (1) ◽  
pp. 353-366 ◽  
Author(s):  
Jiangbo Wan ◽  
Fang Huang ◽  
Siguo Hao ◽  
Weiwei Hu ◽  
Chuanxu Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Cd4 T Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Tr1 Cells

Background/Aims: Tr1 cells can induce peripheral tolerance to self- and foreign antigens, and have been developed as a therapeutic tool for the induction of tolerance to transplanted tissue. We explored the feasibility of generating Tr1 cells by using IL-10 gene-modified recipient DCs (DCLV-IL-10) to stimulate donor naive CD4+ T cells. We also investigated some biological properties of Tr1 cells. Methods: DCLV-IL-10 were generated through DCs transduced with a lentivirus vector carrying the IL-10 gene, and Tr1 cells were produced by using DCLV-IL-10 to stimulate naive CD4+ T cells. The effects of Tr1 cells on T-cell proliferation and the occurrence of graft versus host disease (GVHD) following allogeneic stem-cell transplantation (allo-HSCT) were investigated. Results: The DCLV-IL-10-induced Tr1 cells co-expressed LAG-3 and CD49b. Moreover, they also expressed CD4, CD25, and IL-10, but not Foxp3, and secreted significantly higher levels of IL-10 (1,729.36 ± 185.79 pg/mL; P < 0.001) and INF-γ (1,524.48 ± 168.65 pg/mL; P < 0.01) than the control T cells upon the stimulation by allogeneic DCs. Tr1 cells markedly suppressed T-lymphocyte proliferation and the mixed lymphocytic response (MLR) in vitro. The mice used in the allo-HSCT model had longer survival times and lower clinical and pathological GVHD scores than the control mice. Conclusion: IL-10 gene-modified DC-induced Tr1 cells may be used as a potent cellular therapy for the prevention of GVHD after allo-HSCT.

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