scholarly journals Defective populations of regulatory T cells correlate with the occurrence of chronic graft versus host disease after allogeneic stem cell transplantation

2004 ◽  
Vol 10 ◽  
pp. 20
Author(s):  
E. Zorn ◽  
B. Floyd ◽  
S.J. Lee ◽  
R.J. Soiffer ◽  
J.H. Antin ◽  
...  
Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3745-3758 ◽  
Author(s):  
Emily Blyth ◽  
Leighton Clancy ◽  
Renee Simms ◽  
Chun K. K. Ma ◽  
Jane Burgess ◽  
...  

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.


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 ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jolanta B. Perz ◽  
Selma Gürel ◽  
Stefan O. Schonland ◽  
Ute Hegenbart ◽  
Anthony D. Ho ◽  
...  

Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT) largely relies on the graft-versus-leukemia (GVL) effect. Uncontrolled graft-versus-host disease (GVHD) is a feared complication of HSCT. Regulatory T cells (Treg) are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD) and chronic GVHD (cGVHD).Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls.Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD.Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity.


Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3827-3832 ◽  
Author(s):  
Karen P. Piper ◽  
Claire Horlock ◽  
S. John Curnow ◽  
Julie Arrazi ◽  
Sarah Nicholls ◽  
...  

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.


2017 ◽  
Vol 43 (1) ◽  
pp. 353-366 ◽  
Author(s):  
Jiangbo Wan ◽  
Fang Huang ◽  
Siguo Hao ◽  
Weiwei Hu ◽  
Chuanxu Liu ◽  
...  

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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