Published online
doi:10.1084/jem.20071840
The Journal of Experimental Medicine, Vol. 205, No. 3, 699-710
The Rockefeller University Press, 0022-1007 $30.00
© Jacobsen et al.
Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells
Elizabeth A. Jacobsen1,
Sergei I. Ochkur1,
Ralph S. Pero2,
Anna G. Taranova1,
Cheryl A. Protheroe2,
Dana C. Colbert2,
Nancy A. Lee2, and
James J. Lee1
1 Division of Pulmonary Medicine and 2 Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259
CORRESPONDENCE James J. Lee: jjlee{at}mayo.edu
The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.
Abbreviations used: BAL, bronchoalveolar lavage; i.n., intranasal(ly); i.t., intratracheal(ly); MBP, major basic protein; MDC, macrophage-derived chemokine; TARC, thymus- and activation-regulated chemokine.

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