Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. scid is a loss-of-function mutation of the Prkdc gene that prevents the development of T and B cells. Consequently, macrophages and dendritic cells are defective. The NOD background additionally results in deficient natural killer (NK) cell function. Animals homozygous for the SCID mutation have impaired T and B cell lymphocyte development. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. The NOD genetic background contains alleles that reduce the function of the innate branch of the immune system. NOD SCID Mouse Details The SCID mutation has been transferred onto a non-obese diabetic background. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC "Hu-PBMC mice") are important tools to study human immune function in vivo. This study indicates that both inflammatory and neoplastic conditions contribute to morbidity and mortality in experimentally manipulated aged female NSG mice.Īging background lesions female interleukin-2 receptor gamma chain knockout mouse non-obese diabetic pathology severe combined immunodeficiency.The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. The majority of degenerative lesions that affected the genital tract, endocrine, and skeletal systems did not represent the actual underlying cause of death but rather were considered incidental findings. Novel conditions identified included renal tubular degeneration and necrosis associated with 2 concurrent types of intranuclear inclusions, focal or multifocal hyperostosis of the skull, and neuroendocrine tumors of the mesometrium. Both inflammatory and degenerative lesions of the genital tract were identified, along with neoplasms such as endometrial yolk sac carcinomas and granulosa cell tumors. The major inflammatory conditions were suppurative pleuropneumonia and bronchopneumonia with abscess formation, from which Pasteurella pneumotropica was commonly isolated, followed by otitis media. Malignant mammary neoplasms were most commonly diagnosed, often accompanied by pulmonary metastases, while a low frequency of lymphoma and histiocytic sarcoma was documented. The prevalence of spontaneous morbidity affecting aged NSG female breeders enrolled in a parasitology study was documented with classification of neoplastic and non-neoplastic (inflammatory, metabolic, degenerative) lesions. As a result, these NSG mice lack mature T cells, B cells, or functional NK cells, and are deficient in cytokine. NSG mice combine the features of the NOD/ShiLtJ background, the severe combined immune deficiency mutation ( scid) and IL2 receptor gamma chain deficiency. In the past decade, NOD.Cg- Prkdc scid Il2rg tm1Wjl/SzJ (NSG, NOD scid gamma) mice have become a model of choice in several areas of biomedical research however, comprehensive data on their spontaneous age-related pathology are not currently available in the literature. This strain is only available for Australian and New Zealand researchers.
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