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Impaired thymic negative selection causes autoimmune graft-versus-host disease

Teshima, Takanori ; Reddy, Pavan ; Liu, Chen ; Williams, Debra ; Cooke, Kenneth R. ; Ferrara, JamesL.M.

Blood, 2003-07, Vol.102 (2), p.429-435 [Periódico revisado por pares]

Washington, DC: Elsevier Inc

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Título:
Impaired thymic negative selection causes autoimmune graft-versus-host disease
Autor: Teshima, Takanori ; Reddy, Pavan ; Liu, Chen ; Williams, Debra ; Cooke, Kenneth R. ; Ferrara, JamesL.M.
Assuntos: Adoptive Transfer ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Autoimmune Diseases - etiology ; Autoimmune Diseases - immunology ; Autoimmune Diseases - pathology ; Autoimmune Diseases - prevention & control ; Biological and medical sciences ; Bone Marrow Transplantation - adverse effects ; Bone marrow, stem cells transplantation. Graft versus host reaction ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - transplantation ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - immunology ; Cells, Cultured - immunology ; Clonal Deletion ; Dendritic Cells - immunology ; Epithelial Cells - immunology ; Epithelial Cells - radiation effects ; Female ; Graft vs Host Disease - etiology ; Graft vs Host Disease - immunology ; Graft vs Host Disease - pathology ; Graft vs Host Disease - prevention & control ; Inflammation Mediators - physiology ; Interleukin-1 - physiology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Radiation Chimera ; Radiation Tolerance ; Self Tolerance - immunology ; Skin - pathology ; Spleen - cytology ; T-Lymphocyte Subsets - immunology ; Thymectomy ; Thymus Gland - cytology ; Thymus Gland - immunology ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tumor Necrosis Factor-alpha - physiology ; Viscera - pathology
É parte de: Blood, 2003-07, Vol.102 (2), p.429-435
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Animal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T-cell repertoire. We investigated the requirements for the de velopment of systemic autoimmune disease by using bone marrow chimeras that lacked expression of major histocompatibility complex (MHC) class II on thymic antigen-presenting cells (APCs), leading to impaired negative selection. We found that impaired negative selection mediated by absence of MHC class II, but not MHC class I, permitted the development of systemic autoimmune disease that is indistinguishable from acute graft-versus-host disease (GVHD). Thymectomy prevented disease, confirming the causal association of the thymus with its development. Adoptive transfer of CD4+ T cells caused GVHD in secondary hosts only when they were irradiated, and cotransfer of peripheral CD4+ and CD8+ T cells from naive mice prevented the disease. These results demonstrate that impaired thymic negative selection can cause lethal autoimmune disease indistinguishable from acute GVHD in the context of a proinflammatory milieu when peripheral regulatory mechanisms are absent.
Editor: Washington, DC: Elsevier Inc
Idioma: Inglês

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Impaired thymic negative selection causes autoimmune graft-versus-host disease

Teshima, Takanori ; Reddy, Pavan ; Liu, Chen ; Williams, Debra ; Cooke, Kenneth R. ; Ferrara, JamesL.M.

Washington, DC: Elsevier Inc

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