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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1765-1775
IMMUNOBIOLOGY
Defective development of NK1.1+ T-cell antigen
receptor   + cells in zeta-associated protein 70 null mice with an accumulation of NK1.1+
CD3 NK-like cells in the thymus
Kazuya Iwabuchi,
Chikako Iwabuchi,
Saori Tone,
Daisuke Itoh,
Noriko Tosa,
Izumi Negishi,
Kazumasa Ogasawara,
Toshimitsu Uede, and
Kazunori Onoé
From the Division of Immunobiology and Molecular
Immunology, Institute for Genetic Medicine, Hokkaido University,
Sapporo, Japan.
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+ TCR  + and NK1.1+
TCR  + 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- 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 V14J281 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 TCR and transgenes to the ZAP-70/ mice resulted in generation
of an NK1.1+ TCRdim population, whereas
no substantial CD4+ CD8 or CD4
CD8+ population that expressed the introduced
TCR 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.
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