title: The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.
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.
authors.affiliation: Institute for Medical Immunology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schumann
authors.forename: K
authors.initials: K
authors.lastname: Stanko
authors.forename: S
authors.initials: S
authors.lastname: Woertge
authors.forename: C
authors.initials: C
authors.lastname: Appelt
authors.forename: M
authors.initials: M
authors.lastname: Schumann
authors.forename: A A
authors.initials: AA
authors.lastname: Kühl
authors.forename: I
authors.initials: I
authors.lastname: Panov
authors.forename: U
authors.initials: U
authors.lastname: Schliesser
authors.forename: S
authors.initials: S
authors.lastname: Vogel
authors.forename: S
authors.initials: S
authors.lastname: Ahrlich
authors.forename: M
authors.initials: M
authors.lastname: Vaeth
authors.forename: F
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: A
authors.initials: A
authors.lastname: Waisman
authors.forename: B
authors.initials: B
authors.lastname: Sawitzki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000502:physiology; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000276:immunology* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C543717:TOAG-1 protein, mouse; C064658:RAG-1 protein
keywords: Basic (laboratory) research/science; T cell biology; cellular biology; immunobiology; organ transplantation in general; signaling/signaling pathways; tolerance: experimental