title: The mitochondrial phospholipid cardiolipin is involved in the regulation of T-cell proliferation.
abstract: Challenge of the immune system with antigens induces a cascade of processes including activation of naïve T cells, induction of proliferation, differentiation into effector cells and finally contraction via apoptosis. To meet the dynamic requirements of an adequate immune response, T cells must metabolically adapt to actual situations by switching between catabolic and anabolic metabolism. In this context mitochondria are hubs of metabolic regulation. The phospholipid cardiolipin (CL) is crucial for the structural and functional integrity and, thus, the metabolism of mitochondria. The aim of this study was to verify a possible interrelationship between T cell proliferation and CL composition. For this purpose, we adjusted the proliferation of peripheral human T cells from volunteers by stimulation with different concentrations of the mitogen phytohaemagglutinin (PHA), inhibition with Cyclosporin A (CsA) and exposure of cells to different free fatty acids and subsequently analysed the composition of CL by LC/MS/MS spectroscopy. All of the treatments had significant effects on CL composition. Correlation analysis of the proliferation rate and CL composition revealed that only the amount of incorporated palmitoleic acid and the content of tetralinoleoyl-CL are significantly associated with the proliferation rate. This observation is strongly suggestive of a regulatory function of these particular CL components/species in the process of T cell proliferation. As CL is crucially involved in mitochondrial function one can speculate that changes in CL composition contribute to vital mitochondria-dependent adaptations of energy metabolism in T cells during immune response.
authors.affiliation: Department of Pathological Biochemistry, Otto-von-Guericke University, D-39120 Magdeburg, Germany.
authors.forename: Eik
authors.initials: E
authors.lastname: Mürke
authors.affiliation: Department of Pathological Biochemistry, Otto-von-Guericke University, D-39120 Magdeburg, Germany.
authors.forename: Steffan
authors.initials: S
authors.lastname: Stoll
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, Ernst-Moritz-Arndt-University, D-17475 Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, D-39120 Magdeburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.affiliation: Department of Pathological Biochemistry, Otto-von-Guericke University, D-39120 Magdeburg, Germany. Electronic address: lorenz.schild@med.ovgu.de.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Schild
mesh_terms: D002308:Cardiolipins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D005227:Fatty Acids; D016572:Cyclosporine
keywords: Cardiolipin; Free fatty acids; Proliferation; T-cells