Membrane-Associated Proteinase 3 on Granulocytes and Acute Myeloid Leukemia Inhibits T Cell Proliferation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Tian-Hui YangJeffrey J Molldrem

Abstract

Proteinase 3 (P3), a serine protease expressed by myeloid cells, localized within azurophil granules, and also expressed on the cellular membrane of polymorphonuclear neutrophils (PMN), is the target of autoimmunity in granulomatosis with polyangiitis. PR1, an HLA-A2 restricted nonameric peptide derived from P3, has been targeted effectively in myeloid leukemia. We previously showed (Molldrem et al. 2003. JClinInvest 111: 639-647) that overexpression of P3 in chronic myeloid leukemia induces apoptosis of high-affinity PR1-specific T cells, leading to deletional tolerance and leukemia outgrowth. In this study, we investigated the effect of membrane P3 (mP3)-expressing PMN and acute myeloid leukemia (AML) blasts on the proliferation of CD4 and CD8 T cells in vitro. We demonstrate that mP3-expressing PMN significantly inhibits autologous healthy donor T cell proliferation but does not affect cytokine production in activated T cells and that this effect requires cell proximity and was abrogated by P3 blockade. This inhibition required P3 enzyme activity. However, suppression was not reversed by either the addition of catalase or the inhibition of arginase I. In addition to P3 blockade, anti-low density lipoprotein receptor-related ...Continue Reading

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Mar 23, 2019·Blood·Morgan A GieseAnna Huttenlocher
Mar 20, 2019·Frontiers in Immunology·Ricardo Grieshaber-Bouyer, Peter A Nigrovic
Aug 6, 2019·Frontiers in Immunology·Hans-Heinrich ObergDieter Kabelitz
May 20, 2020·International Journal of Molecular Sciences·Naofumi MukaidaTomohisa Baba
Jun 15, 2019·Journal of Immunology Research·Marco FolciEnrico Brunetta
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Jun 15, 2021·Frontiers in Cardiovascular Medicine·Jiefang ChenLing Mao
May 28, 2019·Experimental Cell Research·Ming-Ming WangJian-Hua Tong

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