Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Blood ; 123(3): 346-55, 2014 Jan 16.
Article in English | MEDLINE | ID: mdl-24196073

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) is causally associated with adult T-cell leukemia (ATL), an aggressive T-cell malignancy with a poor prognosis. To elucidate ATL pathogenesis in vivo, a variety of animal models have been established; however, the mechanisms driving this disorder remain poorly understood due to deficiencies in each of these animal models. Here, we report a novel HTLV-1-infected humanized mouse model generated by intra-bone marrow injection of human CD133(+) stem cells into NOD/Shi-scid/IL-2Rγc null (NOG) mice (IBMI-huNOG mice). Upon infection, the number of CD4(+) human T cells in the periphery increased rapidly, and atypical lymphocytes with lobulated nuclei resembling ATL-specific flower cells were observed 4 to 5 months after infection. Proliferation was seen in both CD25(-) and CD25(+) CD4 T cells with identical proviral integration sites; however, a limited number of CD25(+)-infected T-cell clones eventually dominated, indicating an association between clonal selection of infected T cells and expression of CD25. Additionally, HTLV-1-specific adaptive immune responses were induced in infected mice and might be involved in the control of HTLV-1-infected cells. Thus, the HTLV-1-infected IBMI-huNOG mouse model successfully recapitulated the development of ATL and may serve as an important tool for investigating in vivo mechanisms of ATL leukemogenesis and evaluating anti-ATL drug and vaccine candidates.


Subject(s)
Disease Models, Animal , HTLV-I Infections/immunology , Leukemia-Lymphoma, Adult T-Cell/immunology , AC133 Antigen , Animals , Antigens, CD/metabolism , Bone Marrow/metabolism , CD4-Positive T-Lymphocytes/cytology , Cell Separation , Female , Fetal Blood/metabolism , Flow Cytometry , Glycoproteins/metabolism , Hematopoietic Stem Cells/cytology , Human T-lymphotropic virus 1/immunology , Humans , Inflammation , Interleukin-2 Receptor alpha Subunit/metabolism , Leukemia-Lymphoma, Adult T-Cell/virology , Mice , Mice, Inbred NOD , Peptides/metabolism , Spleen/cytology , Stem Cells/cytology , Viral Load
SELECTION OF CITATIONS
SEARCH DETAIL