6 research outputs found
96 Improved outcome in acute lethal murine graft versus host disease (GVHD) following administration of the proteasome inhibitor PS-341
Growth hormone (GH)-induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome
Adoptive cellular immunotherapy. NK cells and bone marrow transplantation
Allogeneic bone marrow transplantation
(BMT) has been increasingly used for the treatment of
both neoplastic and non-neoplastic disorders. However,
serious obstacles currently limit the efficacy and thus
more extensive use of BMT. These obstacles include:
graft-versus-host disease (GVHD), relapse from the
original tumor, and susceptibility of patients to
opportunistic infections due to the immunosuppressive
effects of the conditioning regimen.Overcoming these
obstacles is complicated by dual outcome of existing
regimens; attempts to reduce GVHD by depleting T cells
from the graft, result in increased rates of tumor relapse
and failure of engraftment. On the other hand, efforts to
increase graft-versus-tumor (GVT) effects of the
transplant also promote GVHD. In this review, the use of
natural killer (NK) cells to overcome some of these
obstacles of allogeneic BMT is evaluated. Adoptive
immunotherapy using NK cells after allogeneic BMT
has several potential advantages. First, NK cells can
promote hematopoiesis and therefore engraftment by
production of hematopoietic growth factors. Second, NK
cells have been shown to prevent the incidence and
severity of GVHD. This has been shown to be at least
partially due to TGF-B, an immunosuppressive cytokine.
Third, NK cells have been shown to augment numerous
anti-tumor effects in animals after BMT suggesting a
vital role of NK cells in mediating GVT effects. Finally,
NK cells have been demonstrated to affect B cell
recovery and function in mice. Therefore, understanding
the mechanisms of beneficial effects of NK cells after
BMT may lead to significant increases in the efficacy of
this procedure
96 Improved outcome in acute lethal murine graft versus host disease (GVHD) following administration of the proteasome inhibitor PS-341
Changes in expression of genes involved in apoptosis in activated human T-cells in response to modeled microgravity
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD)
Haematopoietic stem cell transplantation (HSCT) offers promise for the treatment of haematological and immune disorders, solid tumours, and as a tolerance inducing regimen for organ transplantation. Allogeneic HSCTs engraftment requires immunosuppression and the anti-tumour effects are dependent upon the immune effector cells that are contained within or generated from the donor graft. However, significant toxicities currently limit its efficacy. These problems include: (i) graft-versus-host disease (GVHD) in which donor T cells attack the recipient resulting in multi-organ attack and morbidity, (ii) a profound period of immune deficiency following HSCT, and (iii) donor graft rejection. Currently available methods to prevent or treat GVHD with systemic immunosuppression can lead to impaired immune recovery, increased opportunistic infections, and higher relapse rates. This review will provide an overview of GVHD pathophysiology and discuss the roles of various cells, pathways, and factors in the GVHD generation process and in the preservation of graft-versus-tumour effects. Variables that need to be taken into consideration in attempting to extrapolate preclinical results to the clinical paradigm will be highlighted