Immunomodulatory effects of antigen-pulsed macrophages in a murine model of allergic asthma.
Macrophages (Mphi) play an unique role in the activation and regulation of T cells through their ability to modulate specific costimulatory and cytokine signals. Here we investigated the immunomodulatory effects of allergen presentation by Mphi in a murine model of allergic asthma. Purified peritoneal Mphi were pulsed with ovalbumin (OVA) (OVA-Mphi), or the immunodominant epitope OVA(323-339) (OVA(323-339)-Mphi), and characterized for cell surface markers, cytokine production, and antigen-presenting capacity toward OVA(323-339)-specific DO11.10 T cells. Antigen-pulsed Mphi were injected (intravenously) in OVA-sensitized Balb/c mice that were repeatedly challenged with OVA or saline aerosol. Administration of OVA-Mphi inhibited airway eosinophilia and hyperresponsiveness to methacholine concomitant with a reduced interleukin (IL)-4 and IL-5 production by T cells upon OVA stimulation in vitro. Interestingly, OVA-induced IL-10 levels remained unchanged, whereas interferon-gamma could not be detected. In contrast to OVA-Mphi, OVA(323-339)-Mphi administration had no effects on these asthma manifestations. Additional in vitro studies demonstrated that OVA-Mphi, but not OVA(323-339)-Mphi, produced high levels of IL-10 upon interaction with the DO11.10 T cells. This IL-10 production by the OVA-Mphi was dependent on MHC-TCR and CD86-CD28, but not CD80-CD28 or CD40-CD154 interactions. Our data suggest that IL-10 production by allergen presenting Mphi plays a crucial role in successful immunotherapy.
Janssen
Edith M
EM
Department of Pharmacology and Pathophysiology, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands.
Wauben
Marca H M
MH
Nijkamp
Frans P
FP
van Eden
Willem
W
van Oosterhout
Antoon J M
AJ
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D016535:Bronchial Hyperreactivity; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype
D000276:Adjuvants, Immunologic; D000941:Antigens; D016753:Interleukin-10; D007371:Interferon-gamma; D010047:Ovalbumin