Ligation of CD8 leads to apoptosis of thymocytes that have not undergone positive selection

Proceedings of the National Academy of Sciences of the United States of America
Kristie M GrebeTerry A Potter

Abstract

Thymocytes that are not positively selected are said to undergo "death by neglect." We have found that ligation of CD8, either by antibodies or MHC class I molecules, induces apoptosis of CD4(+)CD8+ double-positive (DP) thymocytes. The susceptibility of thymocytes to CD8-mediated apoptosis is developmentally regulated and confined to a subpopulation of DP thymocytes. Stimulation through CD3 protects thymocytes from CD8-mediated apoptosis. We suggest that during thymocyte development, binding of CD8 to MHC class I molecules without T cell receptor engagement induces apoptosis in immature DP thymocytes. Our data are consistent with a model in which thymocytes that do not survive positive selection undergo "death by instruction" instead of death by neglect.

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Citations

Nov 15, 2006·Molecular and Cellular Biology·Steven J Van DykenJamey D Marth
Apr 20, 2013·Journal of Immunological Methods·Lionel LoubakiRenée Bazin
May 19, 2009·European Journal of Immunology·Raedun L ClarkeTerry A Potter
May 16, 2012·European Journal of Immunology·Zsuzsa SzondyKrisztina Köröskényi
Mar 2, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Linda WooldridgeAndrew K Sewell
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Philmore O HolmanStephen C Jameson
Nov 3, 2005·International Immunology·Charlly KaoStephen C Jameson
Jun 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charlly KaoStephen C Jameson
Jun 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mathew ClementLinda Wooldridge

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis