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

223 Citations (Scopus)

Abstract

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
Volume114
Issue number1
DOIs
StatePublished - Jul 2004
Externally publishedYes

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CD4 Antigens
Cell Membrane
T-Lymphocytes
Antigens
Phenotype
Immune Tolerance
Cell Separation
Regulatory T-Lymphocytes
Respiratory System
Immunosuppression
Maintenance
Inflammation

ASJC Scopus subject areas

  • Medicine(all)

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Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3. / Ostroukhova, Marina; Seguin-Devaux, Carole; Oriss, Timothy B.; Dixon-McCarthy, Barbara; Yang, Liyan; Ameredes, Bill; Corcoran, Timothy E.; Ray, Anuradha.

In: Journal of Clinical Investigation, Vol. 114, No. 1, 07.2004, p. 28-38.

Research output: Contribution to journalArticle

Ostroukhova, M, Seguin-Devaux, C, Oriss, TB, Dixon-McCarthy, B, Yang, L, Ameredes, B, Corcoran, TE & Ray, A 2004, 'Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3', Journal of Clinical Investigation, vol. 114, no. 1, pp. 28-38. https://doi.org/10.1172/JCI200420509
Ostroukhova, Marina ; Seguin-Devaux, Carole ; Oriss, Timothy B. ; Dixon-McCarthy, Barbara ; Yang, Liyan ; Ameredes, Bill ; Corcoran, Timothy E. ; Ray, Anuradha. / Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3. In: Journal of Clinical Investigation. 2004 ; Vol. 114, No. 1. pp. 28-38.
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