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Publication : Defective development of NK1.1+ T-cell antigen receptor alphabeta+ cells in zeta-associated protein 70 null mice with an accumulation of NK1.1+ CD3- NK-like cells in the thymus.

First Author  Iwabuchi K Year  2001
Journal  Blood Volume  97
Issue  6 Pages  1765-75
PubMed ID  11238119 Mgi Jnum  J:68078
Mgi Id  MGI:1932014 Doi  10.1182/blood.v97.6.1765
Citation  Iwabuchi K, et al. (2001) Defective development of NK1.1(+) T-cell antigen receptor alphabeta(+) cells in zeta-associated protein 70 null mice with an accumulation of NK1.1(+) CD3(-) NK-like cells in the thymus. Blood 97(6):1765-75
abstractText  Development of natural killer 1.1(+) (NK1.1(+)) CD3(+) (NK1.1(+) T) cells was analyzed in zeta-associated protein 70 (ZAP-70) null ((-/-)) mice. Both NK1.1(+) TCRalphabeta(+) and NK1.1(+) TCRgammadelta(+) cell populations were absent in the thymus and spleen. By contrast, the number of NK1.1(+) CD3(-) cells was increased in these tissues. The NK1.1(+) CD3(-) thymocytes in ZAP-70(-/-) mice had surface phenotypes in common with NK or NK1.1(+) T cells. However, some of them were discordant either with NK cells or with NK1.1(+) T cells. The NK1.1(+) CD3(-) cells produced interferon-gamma upon stimulation with NK1.1 cross-linking in the presence of interleukin-2 and exhibited a substantial cytotoxicity against YAC-1 cells. Moreover, the generation of NK1.1(+) T cells with invariant Valpha14Jalpha281 chains was induced from the NK1.1(+) CD3(-) thymocytes following stimulation with phorbol myristate acetate and ionomycin in a neonatal thymic organ culture. An introduction of TCRalpha and beta transgenes to the ZAP-70(-/-) mice resulted in generation of an NK1.1(+) TCRalphabeta(dim) population, whereas no substantial CD4(+) CD8(-) or CD4(-) CD8(+) population that expressed the introduced TCRalphabeta was generated in the mainstream T lineage. These findings demonstrate that ZAP-70 kinase is indispensable for the development of NK1.1(+) T cells and that the unique NK1.1(+) CD3(-) thymocytes in ZAP-70(-/-) mice contain immediate precursors of NK1.1(+) T cells. (Blood. 2001;97:1765-1775)
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