title: IFN-alpha subtypes differentially affect human T cell motility.
abstract: The type I IFN family includes 14 closely related antiviral cytokines that are produced in response to viral infections. They bind to a common receptor, and have qualitatively similar biological activities. The physiological relevance of this redundancy is still unclear. In this study, we analyzed and compared the effects of two potent antiviral type I IFNs, IFN-alpha 2 and IFN-alpha 8, on the motility of various populations of human T lymphocytes in vitro. In this study, we show that IFN-alpha 2 induces chemokinesis of both CD4(+) and CD8(+) T cells at various stages of differentiation, and induces functional changes that result in enhanced T cell motility, including up-regulation of the integrins LFA-1 and VLA-4, and subsequently, increased ICAM-1- and fibronectin-dependent migration. In contrast, IFN-alpha 8 did not affect T cell motility, despite having similar antiviral properties and similar effects on the induction of the antiviral protein MxA. However, transcription of other IFN-stimulated genes showed that transcription of these genes is selectively activated by IFN-alpha 2, but not IFN-alpha 8, in T cells. Finally, while the antiviral activity of the two subtypes is inhibited by Abs against the two subunits of the IFN-alpha receptor, the chemokinetic effect of IFN-alpha 2 is selectively blocked by Abs against the A1 receptor subunit. These observations are consistent with the possibility that subtype-specific intracellular signaling pathways are activated by type I IFNs in T lymphocytes.
authors.affiliation: Hepatobiliary Group, Department of Gastroenterology, Queen Mary's School of Medicine and Dentistry at Barts and The Royal London Hospital, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Siti H
authors.initials: SH
authors.lastname: Masri
authors.forename: Rachel
authors.initials: R
authors.lastname: David
authors.forename: Meleri
authors.initials: M
authors.lastname: Jones
authors.forename: Arpita
authors.initials: A
authors.lastname: Datta
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Laura
authors.initials: L
authors.lastname: Runkell
authors.forename: Carole
authors.initials: C
authors.lastname: de Dios
authors.forename: Irene
authors.initials: I
authors.lastname: Sizing
authors.forename: Martha J
authors.initials: MJ
authors.lastname: James
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005353:Fibronectins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039041:Integrin alpha4beta1 / Q000096:biosynthesis / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000235:genetics; D021122:Protein Subunits; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors / Q000737:chemistry; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005353:Fibronectins; C554164:IFNA8 protein, human; D039041:Integrin alpha4beta1; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016169:Lymphocyte Function-Associated Antigen-1; D021122:Protein Subunits; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D053633:Receptor, Interferon alpha-beta; D007372:Interferons