| First Author | Raberger J | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 46 | Pages | 17919-24 |
| PubMed ID | 19004789 | Mgi Jnum | J:142514 |
| Mgi Id | MGI:3821648 | Doi | 10.1073/pnas.0805733105 |
| Citation | Raberger J, et al. (2008) The transcriptional regulator PLZF induces the development of CD44 high memory phenotype T cells. Proc Natl Acad Sci U S A 105(46):17919-24 |
| abstractText | 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 IFNgamma 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 IFNgamma 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. |
