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) |