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-Inducible Protein 10 in the Airway Alters Mucosal Allergic Sensitization in Mice1
*
Department of Pathology and Molecular Medicine and Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada; and
Millennium Pharmaceuticals Inc., Cambridge, MA 02139
Although the preliminary characterization of chemokines and their
receptors has been prolific, comparatively little is known about the
role of chemokines in the evolution of immune responses. We speculate
that the preferential recruitment of a particular immune cell
population has implications for the short- and long-term features of an
adaptive response. To test this hypothesis, we employed
adenovirus-mediated gene transfer to express the Th1-affiliated, CXC
chemokine IFN-
-inducible protein (IP) 10 in the airways of mice
undergoing a mucosal sensitization regimen known to result in a
Th2-polarized allergic response. This resulted in a 
60–75%
inhibition of eosinophils in the bronchoalveolar lavage (BAL); these
inflammatory changes were accompanied by enhanced IFN-, ablated
IL-4, and, peculiarly, unaltered IL-5 and eotaxin levels in the BAL.
The effect of IP-10 expression was shown to be dependent on IFN-, as
there was no statistically significant reduction in BAL eosinophilia in
IFN- knockout mice subjected to the IP-10 intervention. Flow
cytometric analysis of mononuclear cells in the lung revealed a 60%
reduction in the fraction of CD4+ cells expressing T1/ST2,
a putative Th2 marker, and a parallel increase in the proportion
expressing intracellular IFN- following IP-10 treatment. The effect
of IP-10 expression at the time of initial Ag encounter is persistent,
as mice rechallenged with OVA following the resolution of acute
inflammation exhibited reduced eosinophilia and IL-4 in the BAL.
Collectively, these data illustrate that local expression of the
chemokine IP-10 can introduce Th1 phenomena to a Th2-predisposed
context and subvert the development of a Th2
response.
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