Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells
Autor: | Nancy A. Lee, Elizabeth A. Jacobsen, James J. Lee, Sergei I. Ochkur, Dana Colbert, R.S. Pero, Cheryl A. Protheroe, Anna G. Taranova |
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Rok vydání: | 2008 |
Předmět: |
CD4-Positive T-Lymphocytes
Ovalbumin T cell T-Lymphocytes Immunology Mice Transgenic Biology CD8-Positive T-Lymphocytes CCL5 Article 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine Immune system Th2 Cells medicine Immunology and Allergy CCL17 Cytotoxic T cell Animals IL-2 receptor 030304 developmental biology Chemokine CCL22 0303 health sciences Models Immunological Pneumonia Articles Eosinophil respiratory system Allergens Adoptive Transfer 3. Good health Eosinophils Mice Inbred C57BL medicine.anatomical_structure Chemokine CCL17 030215 immunology |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 |
Popis: | 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. |
Databáze: | OpenAIRE |
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