Itk derived signals regulate the expression of Th-POK and controls the development of CD4 T cells.

PloS One
Jianfang HuAvery August

Abstract

T cell development is critically dependent on both the environment and signals delivered by the T cell Receptor (TCR). The Tec family kinase Itk has been suggested to be an amplifier of signals emanating from the TCR and the loss of Itk partially affects most stages of thymopoiesis. Loss of Itk also differentially affects the development of conventional vs. non-conventional or innate memory phenotype T cells. Here, we examine whether these lineage choices are affected by a combination of TCR affinity and Itk by analyzing mice lacking Itk and carrying two TCR transgenes with differing affinities, OT-II and DO11.10. Our results show that developing thymocytes receive a gradient of signals, DO11.10>OT-II>DO11.10/Itk(-/-)>OT-II/Itk(-/-). We also show that the development of CD4(+) T cells is controlled by TCR signaling via Itk, which regulates the expression of the transcription factor, Th-POK, an enforcement factor for CD4 commitment. This results in a reduction in CD4(+) T cell development, and an increase in the development of MHC class II restricted TCR transgenic CD8(+) T cells that resemble non-conventional or innate memory phenotype CD8 T cells. This alteration accompanies increased expression of Runx3 and its target genes E...Continue Reading

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Citations

Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yu QiaoCheong-Hee Chang
Jan 10, 2013·Annual Review of Immunology·Luigi D Notarangelo
Jun 26, 2013·The Journal of Experimental Medicine·Dylan J JohnsonBenjamin G Neel
Aug 8, 2012·International Journal of Circumpolar Health·Amanda J Sheppard, Ross Hetherington
Sep 9, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aimee M Beaulieu, Derek B Sant'Angelo
Aug 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabrina SoloukiAvery August
Feb 5, 2021·Nature·Julia MerkenschlagerMichel C Nussenzweig

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Methods Mentioned

BETA
transgenic
flow cytometry
PMA
PCR

Software Mentioned

Prizm

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