The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.
Am J Transplant
; 14(12): 2723-35, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25363083
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T
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Transplante de Pele
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Linfócitos T Reguladores
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Tolerância ao Transplante
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Proteínas Mitocondriais
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Mitocôndrias
Limite:
Animals
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha