Pepro Tech
Originally published online as doi:10.1189/jlb.0604325 on August 17, 2004

Published online before print August 17, 2004
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
jlb.0604325v1
76/5/1028    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuipers, H.
Right arrow Articles by Lambrecht, B. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuipers, H.
Right arrow Articles by Lambrecht, B. N.
(Journal of Leukocyte Biology. 2004;76:1028-1038.)
© 2004 by Society for Leukocyte Biology

Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization

Harmjan Kuipers*,1, Carlo Heirman{dagger}, Daniëlle Hijdra*, Femke Muskens*, Monique Willart*, Sonja van Meirvenne{dagger}, Kris Thielemans{dagger}, Henk C. Hoogsteden* and Bart N. Lambrecht*

* Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands; and
{dagger} Laboratory of Physiology, Medical School of Vrije Universiteit Brussel, Brussels, Belgium

1 Correspondence: Erasmus MC, Department of Pulmonary Medicine, Room Ee2263, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: h.kuipers{at}erasmusmc.nl

It has been postulated that low-level interleukin (IL)-12 production of antigen-presenting cells is associated with the risk of developing atopic asthma. To study the relationship between IL-12 production capacity of dendritic cells (DCs) and development of T helper type 2 (Th2) responses in the lung, we genetically engineered DCs to constutively overexpress bioactive IL-12. Retrovirally mediated overexpression of IL-12 in DCs strongly polarized naïve ovalbumin (OVA)-specific CD4+ T cells toward Th1 effector cells in vitro. After intratracheal injection, OVA-pulsed IL-12-overexpressing DCs failed to induce Th2 responses in vivo and no longer primed mice for Th2-dependent eosinophilic airway inflammation upon OVA aerosol challenge, readily observed in mice immunized with sham-transfected, OVA-pulsed DCs. Analysis of a panel of cytokines and chemokines in the lung demonstrated that the lack of Th2 sensitization was accompanied by increased production of the Th1 cytokine interferon-{gamma} (IFN-{gamma}), chemokines induced by IFN-{gamma}, and the immunoregulatory cytokine IL-10. When Th2 priming was induced using OVA/alum prior to intratracheal DC administration, DCs constitutively expressing IL-12 were no longer capable of preventing eosinophilic airway inflammation and even enhanced it. These data show directly that high-level expression of IL-12 in DCs prevents the development of Th2 sensitization. Enhancing IL-12 production in DCs should be seen as a primary prevention strategy for atopic disorders. Enhancing IL-12 production in DCs is less likely to be of benefit in already Th2-sensitized individuals.

Key Words: gene therapy • inflammation




This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
H. Kuipers, T. Soullie, H. Hammad, M. Willart, M. Kool, D. Hijdra, H. C. Hoogsteden, and B. N. Lambrecht
Sensitization by intratracheally injected dendritic cells is independent of antigen presentation by host antigen-presenting cells
J. Leukoc. Biol., January 1, 2009; 85(1): 64 - 70.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Jasny, M. Eisenblatter, K. Matz-Rensing, K. Tenner-Racz, M. Tenbusch, A. Schrod, C. Stahl-Hennig, V. Moos, T. Schneider, P. Racz, et al.
IL-12-Impaired and IL-12-Secreting Dendritic Cells Produce IL-23 upon CD154 Restimulation
J. Immunol., May 15, 2008; 180(10): 6629 - 6639.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. Meyts, P. W. Hellings, G. Hens, B. M. Vanaudenaerde, B. Verbinnen, H. Heremans, P. Matthys, D. M. Bullens, L. Overbergh, C. Mathieu, et al.
IL-12 Contributes to Allergen-Induced Airway Inflammation in Experimental Asthma
J. Immunol., November 1, 2006; 177(9): 6460 - 6470.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-J. E. Beavitt, K. W. Harder, J. M. Kemp, J. Jones, C. Quilici, F. Casagranda, E. Lam, D. Turner, S. Brennan, P. D. Sly, et al.
Lyn-Deficient Mice Develop Severe, Persistent Asthma: Lyn Is a Critical Negative Regulator of Th2 Immunity
J. Immunol., August 1, 2005; 175(3): 1867 - 1875.
[Abstract] [Full Text] [PDF]