Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an intensive therapy to cure high-risk haematological malignant disorders, congenital diseases, autoimmune disease and so on. The main complication of HSCT is graft-versus-host disease (GVHD), which can cause the death of recipients and affect the therapeutic effect. Many kinds of immune cells and inflammatory factors were involved in the occurrence of GVHD. Twenty years ago the mice and human interleukin-17 (IL-17) were found. A new kind of T cell-CD4(+) IL-17(+) T was found in recent years, named Th17 cells. Now IL-17 and Th17 cells have become the hot spot in the research field of infection immunity, autoimmune diseases, tumor immunity and GVHD. In this article, immunoregulatory effects of interleukin-17 and Th17 cells in GVHD are reviewed.
Animals ; Graft vs Host Disease ; immunology ; therapy ; Humans ; Immunomodulation ; Interleukin-17 ; immunology ; Mice ; Th17 Cells ; immunology

Mesenchymal stem cells (MSC) are the non-hematopoietic stem cells with a multi-differentiation potentials, which has a low immunogenicity and immune regulation ability. MSC immune regulation ability is particularly important, such as MSC can inhibit the activation and proliferation of T, B lymphocytes, NK cells and dendritic cells (DC). Meanwhile, MSC is able to reconstruct the human hematopoietic microenvironment, improving the successful rate of hematopoietic stem cell transplantation. Graft versus host disease (GVHD) is the main factor causing hematopoietic stem cell transplantation-related mortality. Based on the above mentioned properties, MSCs are used to treat autoimmune diseases and GVHD, recently. Therefore, deep exploration of the cellular immune mechanisms of MSC to treat GVHD is particularly important. This review focuses on progress of research related to treatment of GVHD by MSC immune mechanisms and briefly summarizes the status of the clinical studies.
Graft vs Host Disease ; immunology ; therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; immunology

OBJECTIVETo review the characteristics of regulatory T cells (Tregs) and ex vivo expansion of Tregs for treatment of graft-versus-host disease (GVHD).

DATA SOURCESThe data used in this review were retrieved from PubMed (1970-2013). The terms "ex vivo expansion", "regulatory T cell", and "graft-versus-host disease" were used for literature search.

STUDY SELECTIONThe publications about the characteristics of Tregs, ex vivo expansion of Tregs and clinical applications of Tregs against GVHD were identified, retrieved and reviewed.

RESULTSTregs can be classified as natural Tregs (nTregs) and induced Tregs (iTregs). Both subsets share most Treg features. Given their immunosuppressive property, Tregs have been tested for their capability of preventing GVHD. The bottleneck of Treg therapy is the limited numbers of naturally existing Tregs. To solve this problem, ex vivo expansion of nTregs or iTregs has been executed. The initial data indicate Treg therapy is effective in reducing GVHD without compromising graft-versus-leukemia (GVL).

CONCLUSIONEx vivo expansion of Tregs is a reliable way to prepare sufficient number of Tregs for management of GVHD.

Graft vs Host Disease ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; T-Lymphocytes, Regulatory ; cytology

Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; therapy ; Recurrence

Graft-versus-host disease (GVHD) is mediated by mature donor T cells contained in the hematopoietic stem cell graft. During the development of GVHD, signaling through a variety of costimulatory receptors plays an important role in allogeneic T cell responses. Even though delivery of costimulatory signals is a prerequisite for full activation of donor T cells in the phase of their interactions with host APCs, their involvement with GVHD might occur over multiple stages. Like many other aspects of GVHD, promise of therapeutic interventions with costimulatory pathways has been gleaned from preclinical models. In this review, I summarize some of the advances in roles of costimulatory molecules in GVHD pathophysiology and discuss preclinical approaches that warrant further exploration in the clinic, focusing on novel strategies to delete pathogenic T cells.
Animals ; Graft vs Host Disease/*immunology/metabolism/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; T-Lymphocytes/immunology/metabolism ; Transplantation Immunology/immunology ; Transplantation, Homologous

This study was purposed to investigate the change of Th cell subsets in the patients with acute graft-versus host disease (aGVHD) and to explore its role in the pathogenesis of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 23 patients underwent allo-HSCT were selected for analysis. The aGVHD in patients was diagnosed according to clinical features, and was confirmed by skin biopsy in some patients. The peripheral blood from 23 patients was collected before and after allo-HSCT. The quantitative chenges of Th1 and Th2 cells in peripheral blood samples were detected by using flow cytometry. The results showed that out of 23 patieats the aGVHD occured in 8 patients including 1 case of grade I, 2 case of grade II, 3 cases of grade III; no aGVHD occured in 15 patients. The flow cytometry analysis revealed that the amount of Th1 cells in patients with aGVHD was much higher than that in patients without aGVHD (p < 0.01), the IFN-gamma expression of Th1 cells in patients with aGVHD of grad II - III significantly was higher than that in patients without aGVHD (p < 0.01), meanwhie the IL-4 expression of Th2 cells in patients with aGVHD of grade II - III was significantly lower than that in patients without aGVHD (p < 0.05). Dynamical detection indicated that the Th1 obviously increased before occurrence of aGVHD and before treatment of aGVHD, while the Th1 cells obviously decreased after treatment of aGVHD. The Th1 cells not changed significantly in patients without aGVHD before and after allo-HSCT. It is concluded that Th1 cells obviously increase in patients with aGVHD, this increase is related to aGVHD pathogenesis. Detecting the changes of Th cell subsets in the early stage after allo-HSCT may be contributed to early diagnosis and therapy of aGVHD.
Graft vs Host Disease ; blood ; immunology ; Hematologic Neoplasms ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Th1 Cells ; immunology ; pathology

Severe aplastic anemia (SAA) patients without an HLA-matched sibling donor need alternative treatment options. Umbilical cord blood transplantation (UCBT) has become an alternative means for treating various diseases, but it has not been proved to be a satisfactory method to treat SAA. Here, we report the case of a girl who underwent successful two-unit UCBT after engraftment failure with a single unit. Twounit UCBT is proposed to have better engraftment potential and to offer a better chance of survival, according to some reports. Increased cell dose and graft-versus-graft reaction could contribute to these advantages. With this promising result, two-unit UCBT could be an alternative treatment option for patients with SAA without an HLA-matched donor.
Anemia, Aplastic/diagnosis/*therapy ; Child, Preschool ; *Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease/immunology ; HLA Antigens/immunology ; Histocompatibility ; Humans ; In Situ Hybridization, Fluorescence

In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation (HSCT), including hematopoietic stem cell engraftment and the prevention and treatment of graft-versus-host disease (GVHD), and their therapeutic potential has been reported in numerous clinical trials. Although the safety of clinical application of MSCs is established, further modifications to improve their efficacy are required. In this review, we summarize advances in the potential use of MSCs in HSCT. In addition, we discuss their use in clinical trials of the treatment of GVHD following HSCT, the immunomodulatory capacity of MSCs, and their regenerative and therapeutic potential in the field of HSCT.
Animals ; Chimerism ; Clinical Trials as Topic ; Graft vs Host Disease/immunology/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Immunomodulation ; Mesenchymal Stromal Cells/*cytology/immunology

Anemia, Aplastic ; physiopathology ; therapy ; Child ; Child, Preschool ; China ; Cord Blood Stem Cell Transplantation ; adverse effects ; methods ; Female ; Graft Survival ; Graft vs Host Disease ; etiology ; immunology ; therapy ; HLA Antigens ; blood ; immunology ; Histocompatibility ; immunology ; Histocompatibility Testing ; Humans ; Male ; Treatment Outcome

OBJECTIVETo explore the critical dose of T lymphocyte for preserving graft versus leukemia (GVL) while preventing GVHD in murine acute leukemia model treated with H-2 haploidentical hematopoietic stem cell transplantation (HSCT).

METHODS(C57BL/6 x 615) F1 (H-2bk) mice which was inoculated with L615 cells to develop leukemic murine model was the recipient. The healthy C57BL/6 (H-2b) mice was the donor. CD(34)(+) cells from bone marrow and CD(3)(+)cells from spleen of the donor were purified by miniMACS. The purity of CD(34)(+) cells and CD(3)(+) cells were (81.5 +/- 2.4)% and (95.4 +/- 2.9)% respectively. Sixty-nine recipient mice were divided into seven groups. Group A received no treatment, group B received TBI only, the rest groups were irradiated 9 Gy by (60)Co and transfused 10(5) CD(34)(+) cells or mixed with 10(7) (E), 10(8) (F), 1.5 x 10(8) (G) of CD(3)(+) cells respectively. The mice were raised for 60 days, The cause of death was identified by pathology.

RESULTSAll mice in group E survived more than 60 days being significantly longer than that in the rest groups (p < 0.0001). The chimerisms from donor were 100% in the mice survived > 60 days. Mice died of leukemia relapse in group D and group E were significantly less than those in group C (p < 0.001). Mice died from GVHD in group G were significantly more than those in group E and group F (p < 0.001).

CONCLUSIONSThe leukemia relapse rate was highest in mice that were transplanted with CD(34)(+) cells alone. Those mice transfused with CD(3)(+) T lymphocyte in the graft higher than 10(8) cells died from the GVHD was significantly higher. The inclusive dosage of 5 x 10(7) CD(3)(+) T lymphocyte was enough to separate the GVHD from GVL.

Animals ; Antigens, CD34 ; CD3 Complex ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Host Reaction ; Graft vs Leukemia Effect ; Hematopoietic Stem Cell Transplantation ; methods ; Leukemia, Experimental ; immunology ; therapy ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Recurrence, Local ; prevention & control ; T-Lymphocytes ; immunology