Plasticity of regulatory T cells: Subversion of suppressive function and conversion to enhancement of lung allergic responses

Anthony Joetham, Shigeki Matsubara, Masakazu Okamoto, Katsuyuki Takeda, Nobuaki Miyahara, Azzeddine Dakhama, Erwin W. Gelfand

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Activation of CD4+CD25+Foxp3+ naturally occurring regulatory T cells (nTregs) resulting in suppression of lung allergic responses requires interaction of MHC class I on nTregs and CD8. In the absence of CD8 (CD8-/- recipients), transferred nTregs restored airway hyperresponsiveness, eosinophilic inflammation, and IL-13 levels following allergen exposure. Enhancement of lung allergic responses was accompanied by reduced expression of Foxp3 and increased expression of IL-13 in the transferred nTregs. In CD8-/- recipients pretreated with glucocorticoid-induced TNFR-related protein-ligand Ab, the transferred nTregs maintained high levels of Foxp3 and did not result in altered lung responses. Thus, the regulatory function of nTregs can be subverted by reducing the expression of Foxp3 and following signaling through glucocorticoid-induced TNFR-related protein are converted nTregs into IL-13-producing CD4+ T cells mediating lung allergic responses.

Original languageEnglish
Pages (from-to)7117-7124
Number of pages8
JournalJournal of Immunology
Volume180
Issue number11
DOIs
Publication statusPublished - Jan 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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