Cytokines ; immunology ; Graft vs Host Disease ; immunology ; Humans ; Immune System

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

Hepatocyte growth factor (HGF) is a pleiotropic cytokine, its roles in the physiology and pathology of immune system, have been investigated thoroughly, great deal of data have been documented on its immunoregulatory activity. In this review, according to advance of study on HGF in recent years, the role of HGF in the immune regulation, such as immunoregulatory effects of HGF on T lymphocytes, B lymphocytes and dendritic cell, modulation of HGF on specific humoral and cellular immune response, control of acute GVHD and acceleration of myeloid and immunologic reconstitution in allogenetic bone marrow transplantation models, promotion of tissue repair and regeneration, and alleviation of immune rejection in allogeneic organ transplantation including the heart, liver and kidney transplantation, prevention of grafts from injury as well as applicably useful of HGF in the therapy of autoimmune disorders were summarized.
Animals ; Graft Rejection ; immunology ; prevention & control ; Graft vs Host Disease ; immunology ; prevention & control ; Graft vs Leukemia Effect ; immunology ; Hepatocyte Growth Factor ; physiology ; Humans ; Immunity, Cellular ; 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

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the donor cells present a profound immunization therapy efficiency. Among these effector cells, allo-reactivity natural killer (NK) cell activation are concerned with the graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect. As known, GVHD is primarily a T-cell-mediated event but not initiated by NK cells. NK cells may significantly enhance GVL immune response by using an integration of activating and inhibitory receptors. Allo-reactivity NK cell infusion after allo-HSCT already transits from experiments to clinic. In this review the background on NK cells, and their clinical roles in Allo-HSCT were summarized.
Graft vs Host Disease ; immunology ; Graft vs Leukemia Effect ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; immunology ; Transplantation 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

Migration of donor T cells to the host second lymphoid organs and homing of activated donor T cells into the target tissues play crucial role in the pathophysiology of acute graft-versus-host disease (aGVHD). More deep understanding of the mechanisms for donor T cell migration and homing reveals an important significance in preventing the initiation of aGVHD. In this review, the migration of donor T cells to host second lymphoid organs, homing of donor activated T cells into the target organs, homing of regulating T cells into target organs, the mechanisms of T cell migration and homing in process of aGVHD and its study prospects were summarised.
Cell Movement ; Graft vs Host Disease ; Humans ; Receptors, Lymphocyte Homing ; T-Lymphocytes ; cytology ; immunology

Mesenchymal stem cells (MSCs) are a kind of adult stem cells which have the capability to differentiate into multiple cell types as well as self-renew continuously. Recent studies demonstrate that MSCs are low immunogenic and able to exert immunomodulatory function by various approaches, such as suppression of the lymphocyte proliferation, reduction of the dentritic cell generation, maturation and function, down-regulation of the CTL formation and enhancement of regulatory T-cell proportion. In vivo experiments show that MSC infusion can prolong the survival time of allo-skin graft in baboon and ameliorate experimental autoimmune encephalomyelitis in mice. Successful reports have been documented about clinical application of MSC in the management of graft-versus-host disease. In this review, the immunological characteristics and the immunomodulation functions in vitro and in vivo of MSC were summarized.
Animals ; Graft vs Host Disease ; prevention & control ; Humans ; Immunomodulation ; physiology ; Mesenchymal Stromal Cells ; immunology ; physiology ; T-Lymphocytes, Regulatory ; immunology

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treating of malignant diseases of hematopoietic system or non-malignant proliferative diseases, but the occurrence of graft-versus-host disease (GVHD) limits the success rate of hematopoietic stem cell transplantation. Moreover, chronic graft-versus-host disease (cGVHD) is the main factor affecting the long-term survival rate and life quality of recipient after hematopoietic stem cell transplantation. In this article, the latest research progress of the pathogenesis of cGVHD and related problems are reviewed from the thymus, cytokines, T lymphocyte subsets, B lymphocytes and its secreted antibody.
Chronic Disease ; Graft vs Host Disease ; immunology ; pathology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Transplantation, Homologous

OBJECTIVETo evaluate the relationship of chimerism status of cell subsets with engraftment, occurrence of acute graft versus host disease (aGVHD), graft rejection and disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSChimerism status in peripheral blood (PB) and bone marrow (BM) of 65 patients received allo-HSCT were monitored at regular intervals post-transplant. Fluorescence-activated cell sorter (FACS) was used to sort CD3(+)T lymphocytes in 65 cases, CD3(-)CD56(+)CD16(+)NK cells in 52 cases, CD15(+) granulocytes in 32 cases and CD19(+)B lymphocytes in 20 cases post transplants. The chimerism status of different lineage cells was analyzed by polymerase chain reaction amplification of short tandem repeats (PCR-STR).

RESULTSOn day +7, NK-cells donor chimerism (DC 55.5%) was higher than other cell subsets. T lymphocyte was the latest one to reach complete donor chimerism (CDC) with a median on day +21. Patients whose T lymphocytes donor chimerism was more than 70% on day +7 and more than 95% on day +14 had a high risk for acute aGVHD. In all cases except those with ALL, the decreased DC of T lymphocytes were observed before molecular or hematological relapse occurred.

CONCLUSIONSerial and quantitative T cell chimerism analysis provides a reliable and rapid screening method for the early detection of engraftment, graft rejection, disease relapse and occurrence of aGVHD, therefore, is a prognostic tool to identify patients at high risk of aGVHD and disease relapse following allo-HSCT.

Adolescent ; Adult ; Child ; Chimerism ; Female ; Graft Rejection ; immunology ; Graft vs Host Disease ; immunology ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Recurrence ; T-Lymphocytes ; immunology ; Young Adult