Vogel, Simone Z. and Schlickeiser, Stephan and Jurchott, Karsten and Akyuez, Levent and Schumann, Julia and Appelt, Christine and Vogt, Katrin and Schroeder, Martina and Vaeth, Martin and Berberich-Siebelt, Friederike and Lutz, Manfred B. and Grutz, Gerald and Sawitzki, Birgit (2015) TCAIM Decreases T Cell Priming Capacity of Dendritic Cells by Inhibiting TLR-Induced Ca2+ Influx and IL-2 Production. Journal of Immunology, 1 (194). pp. 3136-3146. ISSN 0022-1767

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Abstract

We previously showed that the T cell activation inhibitor, mitochondrial (Tcaim) is highly expressed in grafts of tolerancedeveloping transplant recipients and that the encoded protein is localized within mitochondria. In this study, we show that CD11c+ dendritic cells (DCs), as main producers of TCAIM, downregulate Tcaim expression after LPS stimulation or in vivo alloantigen challenge. LPS-stimulated TCAIM-overexpressing bone marrow–derived DC (BMDCs) have a reduced capacity to induce proliferation of and cytokine expression by cocultured allogeneic T cells; this is not due to diminished upregulation of MHC or costimulatory molecules. Transcriptional profiling also revealed normal LPS-mediated upregulation of the majority of genes involved in TLR signaling. However, TCAIM BMDCs did not induce Il2 mRNA expression upon LPS stimulation in comparison with Control-BMDCs. In addition, TCAIM overexpression abolished LPS-mediated Ca2+ influx and mitochondrial reactive oxygen species formation. Addition of IL-2 to BMDC–T cell cocultures restored the priming capacity of TCAIM BMDCs for cocultured allogeneic CD8+ T cells. Furthermore, BMDCs of IL-2–deficient mice showed similarly abolished LPS-induced T cell priming as TCAIM-overexpressing wild type BMDCs. Thus, TCAIM interferes with TLR4 signaling in BMDCs and subsequently impairs their T cell priming capacity, which supports its role for tolerance induction.

Item Type:	Article
Keywords:	TCAIM; T Cell Priming Capacity; Dendritic Cells; Inhibiting; TLR-Induced Ca2+ Influx; IL-2; Production;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	10687
Identification Number:	https://doi.org/10.4049/jimmunol.1400713
Depositing User:	Martina Schroeder
Date Deposited:	04 Apr 2019 09:59
Journal or Publication Title:	Journal of Immunology
Publisher:	American Association of Immunologists
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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