期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 46, 页码 17919-17924出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805733105
关键词
innate-like lymphocytes; T cell development; transgenics
资金
- Special Research Area SFB-F23 [SFB-F2305]
- Austrian Science Fund [Y-163]
- Austrian Ministry of Science and Research [P-19930]
- Swedish Science Council
- European Council [FP7]
- EURO-PADnet
Transcriptional pathways controlling the development of CD44(hi) memory phenotype (MP) T cells with innate-like functions are not well understood. Here we show that the BTB (bric-a-brac, tramtrack, broad complex) domain-containing protein promyelocytic leukemia zinc finger (PLZF) is expressed in CD44(hi), but not in CD44(lo), CD4(+) T cells. Transgenic expression of PLZF during T cell development and in CD4(+) and CD8(+) T cells induced a T cell intrinsic program leading to an increase in peripheral CD44(hi) MP CD4(+) and CD8(+) T cells and a corresponding decrease of naive CD44(lo) T cells. The MP CD4(+) and CD8(+) T cells produced IFN gamma upon PMA/ionomycin stimulation, thus showing innate-like function. Changes in the naive versus memory-like subset distribution were already evident in single-positive thymocytes, indicating PLZF-induced T cell developmental alterations. In addition, CD1d-restricted natural killer T cells in PLZF transgenic mice showed impaired development and were severely reduced in the periphery. Finally, after anti-CD3/CD28 stimulation, CD4(+) transgenic T cells showed reduced IL-2 and IFN gamma production but increased IL-4 secretion as a result of enhanced IL-4 production of the CD44(hi)CD62L(+) subset. Our data indicate that PLZF is a novel regulator of the development of CD44(hi) MP T cells with a characteristic partial innate-like phenotype.
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