Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies.

摘要: Acute graft-versus-host disease (GVHD) is a primary T-cell-mediated complication of allogeneic hematopoietic stem cell transplantation (HSCT), occurring when donor-derived T cells are stimulated by host antigen-presenting (APCs), enhanced proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha. Recent data indicate that besides differences in major histocompatibility minor antigens, cytokine gene polymorphisms have predictive value for the GVHD. Patients with high anti-inflammatory IL-10 production been demonstrated to be protected from GVHD while patients TNF-alpha serum levels were more at risk Pharmacological immunosuppression prophylaxis therapy, including unspecific approaches corticosteroids or methotrexate (MTX), well specific therapy cyclosporin A (CsA), tacrolimus (FK506), sirolimus, mycophenolate mofetil (MMF), antithymocyte globulin (ATG), monoclonal antibodies (MAbs) directed against CD3, CD25, CD52, cytotoxic T-lymphocyte antigen (CTLA)-4, CD40 ligand, TNF-alpha, proven effective. on novel techniques selectively deplete alloreactive removal, destruction, anergy induction preserving leukemia-specific T-cell clones suggest clinical benefit these approaches. Gene-modified can depleted CD4+CD25+ regulatory under investigation their ability modulate alloreactivity after HSCT. With better understanding immunopathogenesis acute technical improvement recently described therapeutic approaches, removal naive cells, selection Th2 suicide transduced adoptive transfer use treatment modality may expanded nonhematological entities solid tumors autoimmune disorders.