Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-γ-dependent mechanism

C. Tang, M. D. Inman, N. Van Rooijen, P. Yang, H. Shen, Koichiro Matsumoto, P. M. O'Byrne

Research output: Contribution to journalArticle

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Abstract

In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas the Ag-presenting activity of macrophages has been linked with the development of Th1 phenotype. As an immune switch toward Th1 can protect against Th2-mediated allergic response, this study investigated the capacity of lung macrophages to stimulate Th1 responses during the secondary exposure to inhaled allergen, thereby suppressing Th2-mediated allergic airway inflammation in a murine model of allergic asthma. Following airway macrophage depletion in OVA-sensitized mice, lung T cells defaulted to a phenotype that produced less Th1 (IFN-γ) and more Th2 (IL-4 and IL-5) cytokines, leading to more severe airway hyperreactivity and inflammation after intranasal Ag challenge. After OVA pulsing and adoptive transfer, lung macrophages selectively promoted a Th1 response in Ag-sensitized recipients and did not induce pulmonary eosinophilia. By contrast, OVA pulsing and adoptive transfer of a lung cell preparation, consisting of dendritic cells, B cells, and macrophages, promoted a Th2 response with an associated inflammatory response that was suppressed when macrophages were present and pretreated with IFN-γ, but exacerbated when macrophages were depleted before IFN-γ treatment. In addition, Th1-promoting activity of lung macropbages was not related to the autocrine production of IL-12p40. These results suggest that the Th1-promoting APC activity may be an inherent property of the lung macrophage population, and may play an important role, upon stimulation by IFN-γ, in antagonizing an ongoing Th2 immunity and Th2-dependent allergic responses.

Original languageEnglish
Pages (from-to)1471-1481
Number of pages11
JournalJournal of Immunology
Volume166
Issue number3
Publication statusPublished - Feb 1 2001

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Macrophages
Inflammation
Lung
Adoptive Transfer
Dendritic Cells
Immunity
Interleukin-12 Subunit p40
Pulmonary Eosinophilia
Lung Volume Measurements
Phenotype
Interleukin-5
Interleukin-4
Allergens
Immune System
B-Lymphocytes
Asthma
Cytokines
T-Lymphocytes
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-γ-dependent mechanism. / Tang, C.; Inman, M. D.; Van Rooijen, N.; Yang, P.; Shen, H.; Matsumoto, Koichiro; O'Byrne, P. M.

In: Journal of Immunology, Vol. 166, No. 3, 01.02.2001, p. 1471-1481.

Research output: Contribution to journalArticle

Tang, C. ; Inman, M. D. ; Van Rooijen, N. ; Yang, P. ; Shen, H. ; Matsumoto, Koichiro ; O'Byrne, P. M. / Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-γ-dependent mechanism. In: Journal of Immunology. 2001 ; Vol. 166, No. 3. pp. 1471-1481.
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