PMID: 9547336May 23, 1998Paper

CD3 ligation on immature thymocytes generates antagonist-like signals appropriate for CD8 lineage commitment, independently of T cell receptor specificity

The Journal of Experimental Medicine
M A BassonR Zamoyska

Abstract

The signals that direct differentiation of T cells to the CD4 or CD8 lineages in the thymus remain poorly understood. Although it has been relatively easy to direct differentiation of CD4 single positive (CD4+) cells using combinations of antibodies and pharmacological agents that mimic receptor engagements, equivalent stimuli do not induce efficient maturation of CD8+ cells. Here we report that, irrespective of the MHC-restriction specificity of the TCR, differentiation of mature CD8+ thymocytes can be induced by ligation of CD3 polypeptides on immature thymocytes with a F(ab')2 reagent (CD3fos-F(ab')2). The tyrosine phosphorylation patterns stimulated by CD3fos-F(ab')2 have been shown to resemble those delivered to mature T cells by antagonist peptides, which are known to direct positive selection of CD8+ cells, and we can show that this reagent exhibits potent antagonistic-like activity for primary T cell responses. Our results suggest a distinction in the signals that specify lineage commitment in the thymus. We present a model of thymocyte differentiation that proposes that the relative balance of signals delivered by TCR engagement and by p56lck activation is responsible for directing commitment to the CD8 or CD4 lineages.

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Citations

Nov 9, 2000·Immunology Today·M A Basson, R Zamoyska
Jul 31, 2001·Human Immunology·M TanahashiY Fujii
May 30, 2002·Nature Reviews. Immunology·Ronald N Germain
Aug 22, 2001·The Journal of Experimental Medicine·P KrajL Ignatowicz
Apr 14, 2004·The Journal of Experimental Medicine·Parinaz AliahmadJonathan Kaye
Dec 16, 1998·Immunological Reviews·S M Hedrick, L L Sharp
Dec 16, 1998·Immunological Reviews·S ChanD Mathis
Jun 8, 1999·Annual Review of Immunology·W EllmeierD R Littman
Jun 8, 1999·Annual Review of Immunology·E SebzdaP S Ohashi
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·S C Jameson
Oct 5, 2010·Developmental and Comparative Immunology·Aina-Cathrine ØvergårdSonal Patel
Dec 18, 2008·European Journal of Immunology·Satoshi KomaniwaKeiko Udaka
Mar 5, 2003·Immunological Reviews·José Alberola-Ila, Gabriela Hernández-Hoyos
Feb 7, 2001·Immunity·G Hernández-HoyosJ Alberola-Ila
Apr 17, 2002·Cell·Yoko FujimotoThomas F Tedder
Jul 15, 2003·Nature Immunology·Matilde CanellesB J Fowlkes
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·K HayashiM Satake
Nov 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·F R SantoriS Vukmanovic
Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·James L ClementsLee Ann Garrett-Sinha
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M A BassonR Zamoyska
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shin-Young NaUrsula Bommhardt
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Batu ErmanAlfred Singer
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·U BommhardtT Hünig
Sep 6, 2001·European Journal of Immunology·M Correia-NevesC Benoist
Jun 11, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julie A LucasLeslie J Berg

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