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The Mitochondrial Protein TCAIM Regulates Activation of T Cells and Thereby Promotes Tolerance Induction of Allogeneic Transplants
Author(s) -
Schumann J.,
Stanko K.,
Woertge S.,
Appelt C.,
Schumann M.,
Kühl A. A.,
Panov I.,
Schliesser U.,
Vogel S.,
Ahrlich S.,
Vaeth M.,
BerberichSiebelt F.,
Waisman A.,
Sawitzki B.
Publication year - 2014
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12941
Subject(s) - microbiology and biotechnology , t cell , mitochondrion , effector , cd8 , mitochondrial ros , t cell receptor , cytotoxic t cell , cell , biology , immunology , in vitro , immune system , biochemistry
Primary T cell activation and effector cell differentiation is required for rejection of allogeneic grafts in naïve recipients. It has become evident, that mitochondria play an important role for T cell activation. Expression of several mitochondrial proteins such as TCAIM (T cell activation inhibitor, mitochondrial) is down‐regulated upon T cell receptor triggering. Here we report that TCAIM inhibited spontaneous development of memory and effector T cells. CD4 + T cells from Tcaim knock‐in (KI) mice showed reduced activation, cytokine secretion and proliferation in vitro . Tcaim KI T cells tolerated allogeneic skin grafts upon transfer into Rag‐1 KO mice. CD4 + and CD8 + T cells from these mice did not infiltrate skin grafts and kept a naïve or central memory phenotype, respectively. They were unable to acquire effector phenotype and functions. TCAIM altered T cell activation‐induced mitochondrial distribution and reduced mitochondrial reactive oxygen species (mROS) production. Thus, TCAIM controls T cell activation and promotes tolerance induction probably by regulating TCR‐mediated mitochondrial distribution and mROS production.