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Am J Transplant. 2014 Dec;14(12):2723-35. doi: 10.1111/ajt.12941. Epub 2014 Oct 31.

The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.

Author information

1
Institute for Medical Immunology, Charité University Medicine Berlin, Berlin, Germany.

Abstract

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.

KEYWORDS:

Basic (laboratory) research/science; T cell biology; cellular biology; immunobiology; organ transplantation in general; signaling/signaling pathways; tolerance: experimental

PMID:
25363083
DOI:
10.1111/ajt.12941
[Indexed for MEDLINE]
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