Published ahead of print on May 30, 2003, doi:10.1165/rcmb.2003-0014OC Am. J. Respir. Cell Mol. Biol., Volume 29, Number 5, November 2003, 634-641 A more recent version of this article appeared on November 1, 2003
Submitted on January 16, 2003 Antigen presentation by local macrophages promotes nonallergic airway responses in sensitized miceGwenda Pynaert1,1 Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, University of Ghent, Ghent, Belgium * To whom correspondence should be addressed. E-mail: johan.grooten{at}dmb.rug.ac.be.
Local inflammatory responses involve relocating immune functions generated by previous immunization to confined parts of the body, hence are presumed to reflect the prevailing systemic immune bias. To verify to what extend local antigen-presenting cells (APCs) may modulate immune inflammation, we analyzed the consequences of antigen presentation by macrophages on Th2-dependent airway inflammation in ovalbumin (OVA)-sensitized mice. Contrarily to challenge with free OVA, triggering airway eosinophilia and Th2 cell recruitment, intratracheal instillation of immortalized spleen macrophages (Mf4/4 cells), pulsed with OVA, promoted a nonallergic airway response featuring recruitment of IFN-
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-producing Th1 cells. Combining OVA- Mf4/4 instillation with OVA inhalation strongly reduced airway eosinophilia. Inflammation repression persisted after secondary OVA challenge and depended on the antigen-presenting ability of the macrophages. Arguing against Th1-mediated counter regulation, Th1/Th2 ratios remained unaltered in macrophage-treated/OVA-challenged mice. In contrast, levels of IL-4 and IL-13 mRNA in lung tissue CD4+ T cells were strongly down regulated, indicating a suppression of Th2 cell activation. These results document a role for local macrophages/APCs in controlling the nature and intensity of local immune inflammatory responses. The resulting segregation of systemic and local levels of immune reactivity may enable locally inflammation tolerance; it is a nonallergic airway response despite systemic sensitization.
