Naturally occurring lung CD4+CD25+ T cell regulation of airway allergic responses depends on IL-10 induction of TGF- β1

Anthony Joetham, Katsuyuki Takada, Christian Taube, Nobuaki Miyahara, Satoko Matsubara, Toshiyuki Koya, Yeong Ho Rha, Azzeddine Dakhama, Erwin W. Gelfand

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4+CD25+ T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4 +CD25+ T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-β, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-β, and less severe lung histopathology. Significantly, CD4 +CD25+ T cells isolated from IL-10-/- mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-β levels. By analogy, anti-TGF-β treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4+CD25+ T cells as capable of regulating lung allergic responses in an IL-10- and TGF-β-dependent manner.

Original languageEnglish
Pages (from-to)1433-1442
Number of pages10
JournalJournal of Immunology
Volume178
Issue number3
Publication statusPublished - Feb 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Joetham, A., Takada, K., Taube, C., Miyahara, N., Matsubara, S., Koya, T., Rha, Y. H., Dakhama, A., & Gelfand, E. W. (2007). Naturally occurring lung CD4+CD25+ T cell regulation of airway allergic responses depends on IL-10 induction of TGF- β1. Journal of Immunology, 178(3), 1433-1442.