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Subtypes Differentially Affect Human T Cell Motility1
* Hepatobiliary Group, Department of Gastroenterology, Queen Mary’s School of Medicine and Dentistry at Barts and The Royal London Hospital; and
Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; and
Biogen, Cambridge, MA 02142
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-
2 and IFN-8, on the motility of various populations of human T lymphocytes in vitro. In this study, we show that IFN-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-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-2, but not IFN-8, in T cells. Finally, while the antiviral activity of the two subtypes is inhibited by Abs against the two subunits of the IFN- receptor, the chemokinetic effect of IFN-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.
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