PMID: 9539773May 16, 1998Paper

Alloantigen-induced unresponsiveness in cord blood T lymphocytes is associated with defective activation of Ras

Proceedings of the National Academy of Sciences of the United States of America
P PorcuH E Broxmeyer

Abstract

Human umbilical cord blood T lymphocytes (CBTL) respond to primary allostimulation but they do not proliferate upon rechallenge with alloantigen. Using PKH-26-labeled cells created a proliferative block that was observed only in CBTL that have divided during primary stimulation (PKH-26(dim)) but not in unstimulated (PKH-26(bright)) CBTL. CBTL's secondary unresponsiveness resembles anergy and can be overcome by treatment with phorbol myristate acetate (PMA) and ionomycin or by high doses (50-100 units/ml) of interleukin 2. Addition of interleukin 2 to the primary cultures does not prevent the induction of secondary unresponsiveness. Defective Ras activation is detected in PKH-26(dim) CBTL during secondary response to alloantigen or after antibody-mediated T cell receptor stimulation whereas Ras is activated and proliferation is induced in CBTL during primary alloantigenic stimulation. Upon stimulation with PMA plus ionomycin, PMA plus alloantigen, but not alloantigen plus ionomycin, Ras is activated in PKH-26(dim) CBTL, and the block in proliferation is overcome. Correction of PKH-26(dim) CBTL's proliferative defect correlates with PMA-induced Ras activation, suggesting a defect in the signaling pathway leading to Ras. Ras-indep...Continue Reading

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Citations

Dec 18, 2001·European Journal of Immunology·L M Ribeiro-do-CoutoC J Boog
Feb 28, 2001·Journal of Immunological Methods·M E SheehyD F Nixon
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·V DardalhonN Taylor
Jun 8, 2001·European Journal of Haematology·S El MarsafyE Gluckman
Apr 17, 2007·Journal of Reproductive Immunology·Jaleh ShojaeianAmir Hassan Zarnani
Jan 17, 2004·American Journal of Reproductive Immunology : AJRI·Kelly JanisSusan M Aronica
Feb 26, 2013·American Journal of Reproductive Immunology : AJRI·Fernando F MartinezClaudia C Motran
Aug 6, 2005·Cytotherapy·W Tse, Mj Laughlin
Dec 19, 2014·PLoS Neglected Tropical Diseases·Maria C GuimaroAntonio R L Teixeira
Sep 16, 2003·Journal of Leukocyte Biology·Elisabet CantóSilvia Vidal
Jun 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natacha MerindolHugo Soudeyns
Mar 17, 2004·Cancer Control : Journal of the Moffitt Cancer Center·Marcus O Muench, Alicia Bárcena
Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mahboob H QureshiBeth A Garvy

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