Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells.

Nature Immunology
Jung-Hyun ParkAlfred Singer

Abstract

Immature CD4(+)CD8(+) (double-positive (DP)) thymocytes are signaled via T cell antigen receptors (TCRs) to undergo positive selection and become responsive to intrathymic cytokines such as interleukin 7 (IL-7). We report here that cytokine signaling is required for positively selected thymocytes to express the transcription factor Runx3, specify CD8 lineage choice and differentiate into cytotoxic-lineage T cells. In DP thymocytes genetically engineered to be cytokine responsive, IL-7 signaling induced TCR-unsignaled DP thymocytes to express Runx3 and to differentiate into mature CD8(+) T cells, completely circumventing positive selection. We conclude that TCR-mediated positive selection converts DP cells into cytokine-responsive thymocytes, but it is subsequent signaling by intrathymic cytokines that specifies CD8 lineage choice and promotes differentiation into cytotoxic-lineage T cells.

References

Jan 1, 1995·Advances in Immunology·P J Fink, M J Bevan
Jan 1, 1995·Annual Review of Immunology·S C JamesonM J Bevan
Jan 21, 2000·Experimental Hematology·D Metcalf
Oct 18, 2000·The Journal of Experimental Medicine·J ZhuW E Paul
Nov 26, 2003·Nature Immunology·Masato KuboAkihiko Yoshimura
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joanne Kwan, Nigel Killeen
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·C Justin Van De WieleT Kent Teague
May 25, 2004·Blood·Nahed El KassarRonald E Gress
Aug 11, 2004·The Journal of Experimental Medicine·Tomoo UenoYousuke Takahama
Dec 8, 2004·The Journal of Experimental Medicine·Matthias MerkenschlagerKaren E Brown
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Monica ZamischEllen R Richie
Jul 25, 2007·The Journal of Experimental Medicine·Takeshi EgawaDan R Littman
Sep 9, 2008·Nature Immunology·Sawako MuroiIchiro Taniuchi
Sep 20, 2008·Nature Reviews. Immunology·Alfred SingerJung-Hyun Park
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Nuno L AlvesJames P Di Santo
Mar 6, 2009·Genesis : the Journal of Genetics and Development·John F RepassEllen R Richie
Apr 1, 2009·The Journal of Experimental Medicine·Atsushi HosuiLothar Hennighausen
Apr 21, 2009·Blood Cells, Molecules & Diseases·Takeshi Egawa, Ichiro Taniuchi
Aug 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lie Wang, Rémy Bosselut

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Citations

Dec 14, 2012·Advances in Biological Regulation·Daniel RibeiroJoão T Barata
Aug 7, 2013·Molecular Immunology·Philip C Robinson, Matthew A Brown
Jun 12, 2013·Nature Genetics·UNKNOWN International Genetics of Ankylosing Spondylitis Consortium (IGAS)Matthew A Brown
Jul 12, 2011·Nature Genetics·David M EvansUNKNOWN Wellcome Trust Case Control Consortium 2 (WTCCC2)
Jul 21, 2010·Nature Immunology·Andrea C Carpenter, Rémy Bosselut
Feb 8, 2011·Nature Immunology·Joanne E KonkelWanJun Chen
Feb 19, 2013·Nature Immunology·Michele K Anderson
Dec 20, 2013·Nature Immunology·Steve GerondakisRaelene J Grumont
Feb 17, 2010·Nature Immunology·Nicholas R J Gascoigne
Apr 21, 2010·Nature Immunology·Kensuke Takada, Yousuke Takahama
Apr 11, 2012·Nature Reviews. Rheumatology·John D Reveille
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shizue Tani-ichiKoichi Ikuta
Jul 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Charles SinclairBenedict Seddon
Oct 4, 2011·Briefings in Functional Genomics·Matthew A Brown
Aug 25, 2010·International Immunology·Taku Naito, Ichiro Taniuchi
Feb 4, 2011·Genes & Development·Joseph W LandryCarl Wu
Jul 3, 2010·Science·James P Di Santo
May 24, 2014·International Immunology·Yue RenMasaru Taniguchi
Nov 2, 2011·Cellular and Molecular Life Sciences : CMLS·Melvin Cohn
May 29, 2013·European Journal of Immunology·Brett A LinowesJung-Hyun Park
Oct 23, 2012·Rheumatic Diseases Clinics of North America·Philip C Robinson, Matthew A Brown
Mar 17, 2012·Seminars in Immunology·Rhodri Ceredig, Antonius G Rolink
Mar 17, 2012·Seminars in Immunology·Joonsoo Kang, Mark Coles
Mar 17, 2012·Seminars in Immunology·Changwan HongJung-Hyun Park
Oct 16, 2015·Cellular and Molecular Life Sciences : CMLS·Adam T WaickmanJung-Hyun Park
Feb 22, 2012·Current Opinion in Immunology·Lynn M Heltemes-Harris, Michael A Farrar
Mar 6, 2012·Current Opinion in Immunology·Yumei Xiong, Rémy Bosselut
Jul 16, 2010·Cytokine & Growth Factor Reviews·Fabrizio MatteiDavid F Tough

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