Acute Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; prevention & control ; therapy ; Postoperative Period ; Secondary Prevention

Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation, Homologous ; Treatment Outcome

Dideoxynucleosides ; False Positive Reactions ; Fluorine Radioisotopes ; Fluorodeoxyglucose F18 ; Humans ; Inflammation ; diagnosis ; Neoplasm Staging ; Neoplasms ; diagnosis ; metabolism ; pathology ; radiotherapy ; Positron-Emission Tomography ; methods ; Radiotherapy, Intensity-Modulated ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Treatment Outcome

Sphingosine 1-phosphate (S1P) is an important biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors (GPCRs) to regulate the vital functions of several types of immune cells. The S1P GPCRs suppress both generation of specialized functional cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P is chemotactic to T cells, B cells, dendritic cells, and natural killer cells, the major effect of S1P on the immune system is the regulation of lymphocyte recirculation and tissue distribution by S1P and S1P1. Chemotactic response of CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive activities require S1P. FTY720, a new class of immunomodulator, is rapidly phosphorylated by sphingosine kinase 2 in vivo to form the biologically active phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution and functional activity of T cells, B cells, dendritic cells and regulatory T cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible immunosuppressive efficacy to prevent allograft rejection and treat some autoimmune diseases. In this article, the synthesis and metabolism of S1P, the expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the drugs targeted to S1P GPCRs and their clinical implications are reviewed.
Fingolimod Hydrochloride ; Humans ; Immunomodulation ; physiology ; Lysophospholipids ; immunology ; physiology ; Propylene Glycols ; metabolism ; Receptors, G-Protein-Coupled ; immunology ; physiology ; Sphingosine ; analogs & derivatives ; immunology ; metabolism ; physiology

Non-myeloablative allogeneic hematopoietic stem cell transplantation (NMAT) is brought forward recent years. It is a modified transplant technology. NMAT treats malignant disease by graft versus tumor effect of chimerism after transplantation. The difference between this transplantation and standard allogeneic stem cell transplantation is the conditioning regimen. Non-myeloablative allogeneic stem cell transplantation increased the indication of allogeneic stem cell transplantation. This article focused on the background of this transplantation, the results of animal experimental and clinical research, the advantages and shortages of this transplantation.

Chronic graft-versus-host disease (cGVHD) continues to be a major complication in long-term survivors after allogeneic hematopoietic stem cell transplantation and is the principal cause of morbidity and non-relapse mortality. With the new approaches in the immune mechanisms of cGVHD, the diagnosis, prophylaxis and treatment of cGVHD are involved. This review summarises the current progress of research on cGVHD.
Chronic Disease ; Female ; Graft vs Host Disease ; diagnosis ; etiology ; therapy ; Humans ; Male ; Prognosis ; Risk Factors

Recombinant human granulocyte-colony-stimulating factor (rhG-CSF) can widely regulate human immunologic response. In the protocol of peripheral blood stem/progenitor cell mobilization, rhG-CSF can change the numbers and functions of T cells. Then the results can impact the incidence of graft-versus-host disease after allogeneic peripheral blood stem/progenitor cell transplantation. The regulation of rhG-CSF on T cell is an indirect action which is based on the direct action to monocytes and dendritic cells. The numerous IL-10 secreted by monocytes plays a key role in cytokines production, proliferative response and cytotoxicity of T cells. Endogenous IL-10 can induce high expression of SOCS3 and the SOCS3 is very important for regulating the signal transduction of the activities of T cells. In this review influences of rhG-CSF on T-cells in mobilization process and related mechanisms were elaborated with emphasis.
Blood Donors ; Granulocyte Colony-Stimulating Factor ; pharmacology ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Interleukin-10 ; biosynthesis ; Recombinant Proteins ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; biosynthesis ; T-Lymphocytes ; cytology ; drug effects ; metabolism

LFA-1/ICAM-1 costimulation plays an important role in immunologic reaction of many different T cell populations. After TCR/CD3 complex cross-linking MHC/peptide, LFA-1, expressed on T cell increases a higher affinity and avidity for ICAM-1 rapidly. LFA-1 is a key molecule in formation of the immune synapse. LFA-1/ICAM-1 costimulation can engage various signaling events of T cell by up-regulating the activities of PI 3-kinase, sphingomyelinase, and c-Jun NH2-terminal kinase. With the costimulation of LFA-1/ICAM-1, engagement of TCR molecules results in a significant increase of T cell activities, including higher Th1 cytokines production, strongly proliferative response and higher T cell cytotoxicity.
Animals ; Cytokines ; biosynthesis ; Cytotoxicity, Immunologic ; Humans ; Intercellular Adhesion Molecule-1 ; physiology ; Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1 ; physiology ; Signal Transduction ; T-Lymphocytes ; immunology

To study the biological characteristics of mesenchymal stem cells (MSC) from patients with myelodysplastic syndrome (MDS) and their supportive capacity for hematopoiesis in vitro, MSCs from bone marrow samples of MDS patients were isolated, cultured and expanded. Morphology, immunophenotype, osteoblasts differentiative and proliferative property of MSC and colony forming unit-fibroblast (CFU-F) were measured and analyzed. Mononuclear cells (MNC) of cord blood were plated onto a feeder layer formed by MSC of MDS patient, cells count and CFU-GM production were observed. The results showed that the culture-expanded cells from MDS patients presented a typical fibroblast-like morphology. Cells were positive for SH2 (CD105), SH3 (CD73), Thy-1 (CD90), but negative for CD34 and CD45. After induction, these cells could differentiate into osteoblasts. Their proliferative capacity and CFU-F number were similar to those of MSC from healthy donors. The total cell count and CFU-GM yield in supernatants after culture for 2 weeks were significantly lower than those of control in hematopoiesis supportive experiments in vitro (P < 0.05). It is concluded that the biological characteristics of MSC from bone marrow of MDS patients are not different from those of MSC isolated from bone marrow of normal donors, however, their capacity of hematopoiesis support in vitro are significantly weaker.
5'-Nucleotidase ; analysis ; Adult ; Aged ; Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Bone Marrow Cells ; cytology ; immunology ; Cell Differentiation ; Endoglin ; Female ; Hematopoiesis ; Humans ; Male ; Mesenchymal Stromal Cells ; cytology ; immunology ; Middle Aged ; Myelodysplastic Syndromes ; blood ; Receptors, Cell Surface ; analysis

As a functionally and phenotypically distinctive T cell subpopulation, CD4+CD25+ regulatory T cells are anergic and retain their ability to suppress antigen-driven response of CD4+CD25- cells in a contact-dependent manner or through a way of secreting immunosuppressive cytokines such as IL-10 and TGF-beta. Graft-versus-host disease (GVHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (HSCT). Recently, some researches on the relationship between donor CD4+CD25+ regulatory T cells and GVHD severity produced two contradictory conclusions: one is CD4+CD25+ regulatory T cells that can prevent GVHD efficiently; the other is that GVHD is associated with the increased numbers of peripheral blood CD4+CD25+ regulatory T cells. The answer to this question will provide a new idea for clinic therapy of GVHD. In this review some new research progresses in the related area, such as the CD4+CD25+ regulatory T cells, the phenotype, characteristics, immunoregulatory mechanisms of CD4+CD25+ regulatory T cells, as well as the relation of CD4+CD25+ with GVHD were presented.
CD4 Antigens ; analysis ; Graft vs Host Disease ; etiology ; immunology ; Humans ; Interleukin-2 Receptor alpha Subunit ; analysis ; T-Lymphocytes, Regulatory ; cytology ; immunology ; metabolism