title: Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis.
abstract: Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1β, TNF, IFN-γ, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3+ T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NFκB signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Saksida
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljkovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Timotijevic
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojanovic
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatovic
authors.forename: Paolo
authors.initials: P
authors.lastname: Fagone
authors.forename: Katia
authors.initials: K
authors.lastname: Mangano
authors.forename: Santa
authors.initials: S
authors.lastname: Mammana
authors.forename: Claudio
authors.initials: C
authors.lastname: Farina
authors.forename: Ester
authors.initials: E
authors.lastname: Ascione
authors.forename: Valentina
authors.initials: V
authors.lastname: Maiello
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stosic-Grujicic
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000008:administration & dosage / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014168:Transferrin / Q000008:administration & dosage / Q000502:physiology*
chemical_list: D001059:Apoproteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016328:NF-kappa B; D014168:Transferrin; C028284:apotransferrin
keywords: Apotransferrin; Experimental autoimmune encephalomyelitis; IL-2; T cell activation