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Oxidized ATP inhibits T-cell-mediated autoimmunity

Lang, Philipp A.
Funkner, Pauline
Shaabani, Namir
Meryk, Andreas
Krings, Caroline
Barthuber, Carmen
Recher, Mike
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Published in European Journal of Immunology. 2010, vol. 40, no. 9, p. 2401-2408
Abstract T cells directed against self antigens play an important role in several autoimmune diseases. The available immunosuppressive compounds used to treat autoimmune diseases are limited, and often they have side effects that limit their application. T cells express ATP receptors, which could be new target molecules to treat autoimmune disease. Here we analyzed the effect of oxidized ATP (oxATP), an inhibitor of the ATP receptor P2rx7, in different murine models of T-cell-mediated autoimmune diseases. Treatment with oxATP inhibited proliferation and effector function of T cells. In the systems we used, oxATP did not obviously interfere with the innate immune response, but strongly reduced antigen-specific T-cell responses. This treatment ameliorated T-cell-mediated autoimmune type I diabetes and autoimmune encephalitis in mice. In conclusion, oxATP was found to strongly inhibit activated T cells and could thus be used to target T-cell-mediated autoimmune disease.
Keywords Adenosine Triphosphate/administration & dosage/*analogs & derivativesAnimalsApoptosis/drug effects/immunologyAutoimmunity/drug effectsCD4-Positive T-Lymphocytes/*drug effects/immunology/metabolism/pathologyCD8-Positive T-Lymphocytes/*drug effects/immunology/metabolism/pathologyCell Proliferation/drug effectsCells, CulturedCytotoxicity, Immunologic/drug effectsDiabetes Mellitus, Type 1/drug therapy/immunology/*metabolism/pathologyDisease Models, AnimalEncephalomyelitis, Autoimmune, Experimental/drugTherapy/immunology/pathology/physiopathologyFemaleInterferon-gamma/biosynthesis/geneticsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, Purinergic P2/genetics/metabolismReceptors, Purinergic P2X7Spinal Cord/*drug effects/pathology
PMID: 20683833
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Research group La Sclérose en plaques (908)
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LANG, Philipp A. et al. Oxidized ATP inhibits T-cell-mediated autoimmunity. In: European Journal of Immunology, 2010, vol. 40, n° 9, p. 2401-2408. doi: 10.1002/eji.200939838 https://archive-ouverte.unige.ch/unige:21069

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Deposited on : 2012-05-23

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