| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
* Plastic Surgery Unit, Regional Melanoma Referral Center, Tuscan Tumor Institute (ITT), Santa Maria Annunziata Hospital, Florence, Italy;
Department of Dermatological Sciences,
Division of Hematology, and
Department of Pharmacology, University of Florence, Florence, Italy; and
¶ Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
IFN-
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- effects on PBMC in terms of dendritic cell (DC) differentiation, as PBMC are exposed to high IFN- levels during treatment of infections and cancers. We show that in vitro IFN- exposure induced rapid and strong up-regulation of the DC-maturation markers CD80, CD86, and CD83 in bulk PBMC. Consistently, IFN- induced up-regulation of these molecules on purified monocytes within 24 h. Up-regulation of CD80 and CD83 expression was IFN- concentration-dependent. In contrast to GM-CSF + IL-4-generated DCs, most of the IFN--challenged CD83+ cells coexpressed the monocyte marker CD14. Despite a typical mature DC immunophenotype, IFN--treated monocytes conserved phagocytic activity and never acquired a dendritic morphology. In mixed lymphocyte reactions IFN--treated monocytes were less potent than GM-CSF + IL-4-generated DCs but significantly more potent than untreated monocytes to induce T cell proliferation in bulk PBMC. However, only GM-CSF + IL-4-generated DCs were able to induce a significant proliferation of naive CD4+ T cells. Notably, autologous memory CD4+ T cells proliferated when exposed to tetanus toxoid-pulsed IFN--treated monocytes. At variance with untreated or GM-CSF + IL-4-exposed monocytes, those challenged with IFN- showed long-lasting STAT-1 phosphorylation. Remarkably, CD83+CD14+ cells were present in varicella skin lesions in close contact with IFN--producing cells. The present findings suggest that IFN- alone promptly generates nondendritic APCs able to stimulate memory immune responses. This may represent an additional mode of action of IFN- in vivo.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 G.G. is supported by a grant from the Fioravanti family. G.M. and P.D.G. are supported by a grant from the Ente Cassa di Risparmio di Firenze.
2 Address correspondence and reprints request to Dr. Gianni Gerlini, Plastic Surgery Unit-Regional Melanoma Referral Center, Tuscan Tumor Institute (ITT), Santa Maria Annunziata Hospital, Via Antella, 58, I-50011, Florence, Italy. E-mail address: g.gerlini{at}dfc.unifi.it
3 Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; pDC, plasmacytoid dendritic cell; anti-Lin-1, anti-lineage cocktail 1; ST-DC, standard-DCs; IFN-MO, IFN-monocytes; 7-AAD, 7-aminoactinomycin D; IRF-1, interferon responsive factor-1; MFI, mean fluorescence intensity; SLE, systemic lupus erythematodes.
This article has been cited by other articles:
|
|
 |
|
  J. A. Poole, G. M. Thiele, N. E. Alexis, A. M. Burrell, C. Parks, and D. J. Romberger Organic dust exposure alters monocyte-derived dendritic cell differentiation and maturation Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L767 - L776. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
