Natural Foxp3+ regulatory T cells inhibit Th2 polarization but are biased toward suppression of Th17-driven lung inflammation

Teri Girtsman, Zeina Jaffar, Maria Ferrini, Pamela Shaw, Kevan Roberts

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

nTregs prevent autoimmunity and modulate immune and inflammatory responses to foreign antigens. CD4+Foxp3+ nTregs from DO11.10 mice were expanded ex vivo, and their effectiveness in suppressing the development of lung inflammatory responses, elicited by differentiated CD4+ T cells following antigen inhalation, was examined. Effector DO11.10 CD4+ Th2 cells, when adoptively transferred into BALB/c mice that subsequently inhaled OVA, elicited a pronounced pulmonary, eosinophilic inflammation. Surprisingly, the cotransfer of expanded nTregs failed to suppress the Th2-mediated airway inflammation. Nevertheless, expanded OVAspecific CD4 +Foxp3+ nTregs were highly effective at inhibiting the polarization of naïve CD4+ T cells into a Th2 phenotype. This suppression was reversed by an antibody to GITR but was not affected by the presence of the soluble OX40L. Further analysis revealed that although nTregs also failed to inhibit the lung neutrophilic inflammation induced by effector CD4+ Th1 cells, they markedly suppressed pulmonary inflammation elicited by CD4+ Th17 cells but not AHR. The suppression of the Th17-mediated response was evident from a striking reduction in the proportion of OVA-specific T cells expressing IL-17 and the numbers of neutrophils present in the airways of Th17 recipient mice. Collectively, these results demonstrate that expanded nTregs clearly limit the Th2 polarization process and that Th17-mediated inflammatory responses are particularly prone to the immunoregulatory properties of nTregs. These findings thus indicate that expanded nTregs are restrictive in their ability to suppress airway inflammatory processes and AHR.

Original languageEnglish
Pages (from-to)537-546
Number of pages10
JournalJournal of Leukocyte Biology
Volume88
Issue number3
DOIs
StatePublished - Sep 2010

Keywords

  • Airway inflammation
  • CD4
  • Regulation
  • nTregs

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