CD45 tyrosine phosphatase controls common gamma-chain cytokine-mediated STAT and extracellular signal-related kinase phosphorylation in activated human lymphoblasts: inhibition of proliferation without induction of apoptosis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Norbert BlankH M Lorenz

Abstract

The objective of this study was to test whether CD45 signals can influence signaling processes in activated human lymphoblasts. To this end, we generated lymphoblasts which proliferate in response to common gamma-chain cytokines, but readily undergo apoptosis after cytokine withdrawal. In experiments with the CD45R0 mAb UCHL-1, but not control CD45 mAbs, we found significant inhibition of proliferation. Interestingly, the pan-CD45 mAb GAP8.3, which is most effective in inhibition of OKT-3-mediated proliferation in quiescent lymphocytes, was ineffective in lymphoblasts. Addition of CD3 mAb OKT-3 had no influence on IL-2-mediated proliferation (with or without UCHL-1). In contrast, after addition of OKT-3 to IL-4- and IL-7-stimulated proliferation assays, UCHL-1 signals could not significantly alter cellular proliferation. We did not find induction of apoptosis following CD45R0 signaling. In Western blots using mAbs detecting phosphorylated STAT-3, STAT-5, STAT-6, or extracellular signal-related kinase 1/2, we found that CD45R0 signaling could effectively diminish phosphorylation of these intracellular signaling components. Using RT-PCR, we found that CD45R0 signaling inhibited IL-2 mRNA production without major influence on IL-1...Continue Reading

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Citations

Feb 26, 2004·International Journal of Hematology·Qun ZhouSolveig G Ericson
May 1, 2004·The Journal of Experimental Medicine·Martin A KriegelHanns-Martin Lorenz
Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hyeon-Sook SuhSunhee C Lee
Oct 13, 2006·The American Journal of Gastroenterology·Mahefatiana AndrianifahananaSurinder K Batra
Apr 5, 2003·The Journal of Biological Chemistry·Francisco J SalgadoMontserrat Nogueira
Jan 31, 2003·The Journal of Biological Chemistry·Jacob RachmilewitzMark L Tykocinski
Mar 4, 2008·International Immunology·Martin A KriegelHanns-Martin Lorenz
Oct 27, 2009·Apoptosis : an International Journal on Programmed Cell Death·Geneviève Dupéré-MinierJacques Bernier

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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