Induction of NK1.1(+) alpha beta TCR(+) T cells by bypassing TCR signals in ZAP-70 deficient mice.
The mechanism of development of a unique subset of T cells, thymic NK1.1(+) alpha beta T cells, has been poorly understood. We found that the development of thymic NK1.1(+) alpha beta T cells was defective in mice deficient in ZAP-70. Instead, an accumulation of NK1.1(+) TCR beta(-) NK-like population was detected in the thymus and spleen of the ZAP-70 deficient (ZAP -/-) mouse. In the present report, we examined whether biochemical treatments that replace TCR-mediated positive selection signals could restore the generation of thymic NK1.1(+) alpha beta T cells in ZAP -/- mice using the thymus organ culture. We found that a higher concentration of phorbol ester (PMA) than that required for CD4(+) T cell generation and ionomycin induced the generation of NK1.1(+) alpha beta T cells. Phenotypic analysis of the induced NK1.1(+) alpha beta T cell population suggested that these cells expressed CD8 but not CD4 molecules, which is a different characteristic from ordinary thymic NK1.1(+) alpha beta T cells. These results suggest that differential signaling is required for the generation of mainstream T cells and thymic NK1.1(+) alpha beta T cells.
Tone
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Division of Immunobiology, Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-Ku, Sapporo 060-0815, Japan.
Iwabuchi
K
K
Iwabuchi
C
C
Negishi
I
I
Onoé
K
K
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000187:drug effects / Q000378:metabolism*; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009924:Organ Culture Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D007476:Ionophores; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010703:Phorbol Esters; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015759:Ionomycin; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse