Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3

Marina Ostroukhova, Carole Seguin-Devaux, Timothy B. Oriss, Barbara Dixon-McCarthy, Liyan Yang, Bill Ameredes, Timothy E. Corcoran, Anuradha Ray

Research output: Contribution to journalArticle

227 Scopus citations


Under normal circumstances, the respiratory tract maintains immune tolerance in the face of constant antigen provocation. Using a murine model of tolerance induced by repeated exposure to a low dose of aerosolized antigen, we show an important contribution by CD4+ T cells in the establishment and maintenance of tolerance. The CD4+ T cells expressed both cell surface and soluble TGF-β and inhibited the development of an allergic phenotype when adoptively transferred to naive recipient mice. While cells expressing cell surface TGF-β were detectable in mice with inflammation, albeit at a lower frequency compared with that in tolerized mice, only those from tolerized mice expressed FOXP3. Blockade of TGF-β in vitro and in vivo interfered with immunosuppression. Although cells that expressed TGF-β on the cell surface (TGF-β+), as well as the ones that did not (TGF-β-), secreted equivalent levels of soluble TGF-β, only the former were able to blunt the development of an allergic phenotype in mice. Strikingly, separation of the TGF-β+ cells from the rest of the cells allowed the TGF-β- cells to proliferate in response to antigen. We propose a model of antigen-induced tolerance that involves cell-cell contact with regulatory CD4+ T cells that coexpress membrane-bound TGF-β and FOXP3.

Original languageEnglish (US)
Pages (from-to)28-38
Number of pages11
JournalJournal of Clinical Investigation
Issue number1
StatePublished - Jul 2004
Externally publishedYes


ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ostroukhova, M., Seguin-Devaux, C., Oriss, T. B., Dixon-McCarthy, B., Yang, L., Ameredes, B., Corcoran, T. E., & Ray, A. (2004). Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3. Journal of Clinical Investigation, 114(1), 28-38.