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 developm ent of thymic NK1.1(+) alpha beta T cells was defective in mice deficient i n ZAP-70. Instead, an accumulation of NK1.1(+) TCR beta(-) NK-like populati on was detected in the thymus and spleen of the ZAP-70 deficient (ZAP -/-) mouse. In the present report, we examined whether biochemical treatments th at replace TCR-mediated positive selection signals could restore the genera tion 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 induc ed NK1.1(+) alpha beta T cell population suggested that these cells express ed CD8 but not CD4 molecules, which is a different characteristic from ordi nary thymic NK1.1(+) alpha beta T cells. These results suggest that differe ntial signaling is required for the generation of mainstream T cells and th ymic NK1.1(+) alpha beta T cells. (C) 2000 Elsevier Science B.V. All rights reserved.