Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta.
Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4(+)CD25(+) T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4(+)CD25(+) T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-beta, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-beta, and less severe lung histopathology. Significantly, CD4(+)CD25(+) T cells isolated from IL-10(-/-) mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-beta levels. By analogy, anti-TGF-beta treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4(+)CD25(+) T cells as capable of regulating lung allergic responses in an IL-10- and TGF-beta-dependent manner.
Joetham
Anthony
A
Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Takeda
Katsuyuki
K
Takada
Katsuyuki
K
Taube
Christian
C
Miyahara
Nobuaki
N
Matsubara
Shigeki
S
Matsubara
Satoko
S
Koya
Toshiyuki
T
Rha
Yeong-Ho
YH
Dakhama
Azzeddine
A
Gelfand
Erwin W
EW
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006967:Hypersensitivity / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10