An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation.
A T helper cell type 1-mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RB(high) CD4(+) T cells and can be prevented by cotransfer of the CD45RB(low) subset. The immune-suppressive activities of the CD45RB(low) T cell population can be reversed in vivo by administration of an anti-transforming growth factor beta antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RB(low) population. This population isolated from IL-10-deficient (IL-10(-/-)) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti-murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RB(low) CD4(+) cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RB(high) CD4(+) cells, as CD45RB(low) CD4(+) cells from WT mice were able to inhibit colitis induced by IL-10(-/-) CD45RB(high) CD4(+) cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.
Asseman
C
C
Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom.
Mauze
S
S
Leach
M W
MW
Coffman
R L
RL
Powrie
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D003108:Colonic Diseases / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016212:Transforming Growth Factor beta; C064655:V(D)J recombination activating protein 2; D016753:Interleukin-10; D007371:Interferon-gamma