Antigen specificity is not required for modulation of lung allergic responses by naturally occurring regulatory T cells.
Naturally occurring Foxp3(+)CD4(+)CD25(+) T cells isolated from lungs of naive mice regulate lung allergic airway hyperresponsiveness, inflammation, levels of Th2 cytokines, and mucus production. OVA-specific (alphabetaTCR(+)) CD4(+)CD25(+) T cells suppressed ragweed-induced airway hyperresponsiveness and inflammation as did anti-TCR-treated OVA-specific CD4(+)CD25(+) T cells, suggesting that Ag-specificity was not required for expression of regulatory activities. Suppression was associated with increased levels of IL-10 and TGF-beta; decreased levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid; and reduced recruitment and activation of CD8(+) T cells in the airways. Following intratracheal administration, OVA-specific CD4(+)CD25(+) T cells were identified in both the airway lumens and lung parenchyma, and in some instances in close proximity to host CD8(+) T cells. These results demonstrate that the regulatory activities of naturally occurring Foxp3(+)CD4(+)CD25(+) T cells on lung allergic responses are Ag-nonspecific and thus, independent of Ag-specific recognition.
Joetham
Anthony
A
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
Takeda
Katsuyuki
K
Okamoto
Masakazu
M
Taube
Christian
C
Matsuda
Hiroyuki
H
Dakhama
Azzeddine
A
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D016207:Cytokines / Q000032:analysis; D000939:Epitopes / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation; D008171:Lung Diseases / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; D010047:Ovalbumin