Cellular and cytokine effectors of acute graft versus host disease. 2002

James L M Ferrara

Graft-versus-host-disease (GVHD) is the major complication of allogeneic Bone Marrow Transplant (BMT) and Older BMT recipients are at greater risk for acute graft-versus-host-disease. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older recipients. GVHD mortality and morbidity, as well as pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs) from old mice. In a haploidential GVHD model, CD4+ donor T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using B6D2FI BM chimeras created with either old or young BM. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. We also evaluated whether alloantigen expression on host target epithelium is essential for tissue damage induced by GVHD in mouse models. In bone marrow chimeras recipients in which either MHC II or MHC I alloantigen was expressed only on APCs, we found that acute GVHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GVHD. These results suggest new strategies for the prevention and treatment of this toxic complication of BMT.

UI MeSH Term Description Entries
D007111 Immunity, Cellular Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Cell-Mediated Immunity,Cellular Immune Response,Cell Mediated Immunity,Cell-Mediated Immunities,Cellular Immune Responses,Cellular Immunities,Cellular Immunity,Immune Response, Cellular,Immune Responses, Cellular,Immunities, Cell-Mediated,Immunities, Cellular,Immunity, Cell-Mediated,Response, Cellular Immune
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006086 Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D000208 Acute Disease Disease having a short and relatively severe course. Acute Diseases,Disease, Acute,Diseases, Acute
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000938 Antigen-Presenting Cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors. Accessory Cells, Immunologic,Antigen-Presenting Cell,Immunologic Accessory Cells,Accessory Cell, Immunologic,Cell, Immunologic Accessory,Cells, Immunologic Accessory,Immunologic Accessory Cell,Antigen Presenting Cell,Antigen Presenting Cells,Cell, Antigen-Presenting,Cells, Antigen-Presenting
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D016026 Bone Marrow Transplantation The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION. Bone Marrow Cell Transplantation,Grafting, Bone Marrow,Transplantation, Bone Marrow,Transplantation, Bone Marrow Cell,Bone Marrow Grafting

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