ABSTRACT. Interferon (IFN)-α is a well known agent for treatment of viral and malignant diseases. It has several modes of actions, including direct influence on the immune system. We investigated IFN-α effects on peripheral blood mononuclear cells (PBMC) in terms of dendritic cell (DC) differentiation, as PBMC are exposed to high IFN-α levels during treatment of infections and cancers. We show that in vitro IFN-α exposure induced rapid and strong up-regulation of the DC-maturation markers CD80, CD86 and CD83 in bulk PBMC. Consistently, IFN-α induced up-regulation of these molecules on purified monocytes within 24 h. Up-regulation of CD80 and CD83 expression was IFN-α-concentration dependent. In contrast to GM-CSF+IL-4 generated DCs, most of the IFN-α-challenged CD83+ cells co-expressed the monocyte marker CD14. Despite a typical DC immunophenotype, cells never acquired a dendritic morphology. In mixed lymphocyte reactions IFN-α treated monocytes were significantly more potent than untreated monocytes to induce T-cell proliferation. At variance with untreated or GM-CSF+IL-4-exposed monocytes, IFN-α-challenged monocytes showed long-lasting STAT-1 phosphorylation. Remarkably CD83+CD14+ cells were present in varicella skin lesions in close contact with IFN-α-producing cells. The present findings suggest that IFN-α alone promptly generates non-dendritic antigen-presenting cells. This may represent an additional mode of action of IFN-α in vivo.

Induction of CD83+ CD14+ non-dendritic antigen-presenting cells by exposure of monocytes to IFN-alpha1 / G. Gerlini; G. Mariotti; A. Chiarugi; P. Di Gennaro; R. Caporale; A. Parenti; L. Cavone; A. Tun-Kyi; F. Prignano; R. Saccardi; L. Borgognoni; N. Pimpinelli. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - STAMPA. - 181(5):(2008), pp. 2999-3008.

Induction of CD83+ CD14+ non-dendritic antigen-presenting cells by exposure of monocytes to IFN-alpha1

GERLINI, GIANNI;MARIOTTI, GIULIA;CHIARUGI, ALBERTO;PARENTI, ASTRID;F. Prignano;PIMPINELLI, NICOLA
2008

Abstract

ABSTRACT. Interferon (IFN)-α is a well known agent for treatment of viral and malignant diseases. It has several modes of actions, including direct influence on the immune system. We investigated IFN-α effects on peripheral blood mononuclear cells (PBMC) in terms of dendritic cell (DC) differentiation, as PBMC are exposed to high IFN-α levels during treatment of infections and cancers. We show that in vitro IFN-α exposure induced rapid and strong up-regulation of the DC-maturation markers CD80, CD86 and CD83 in bulk PBMC. Consistently, IFN-α induced up-regulation of these molecules on purified monocytes within 24 h. Up-regulation of CD80 and CD83 expression was IFN-α-concentration dependent. In contrast to GM-CSF+IL-4 generated DCs, most of the IFN-α-challenged CD83+ cells co-expressed the monocyte marker CD14. Despite a typical DC immunophenotype, cells never acquired a dendritic morphology. In mixed lymphocyte reactions IFN-α treated monocytes were significantly more potent than untreated monocytes to induce T-cell proliferation. At variance with untreated or GM-CSF+IL-4-exposed monocytes, IFN-α-challenged monocytes showed long-lasting STAT-1 phosphorylation. Remarkably CD83+CD14+ cells were present in varicella skin lesions in close contact with IFN-α-producing cells. The present findings suggest that IFN-α alone promptly generates non-dendritic antigen-presenting cells. This may represent an additional mode of action of IFN-α in vivo.
2008
181(5)
2999
3008
G. Gerlini; G. Mariotti; A. Chiarugi; P. Di Gennaro; R. Caporale; A. Parenti; L. Cavone; A. Tun-Kyi; F. Prignano; R. Saccardi; L. Borgognoni; N. Pimpinelli
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/329147
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