Steady-state migrating intestinal dendritic cells induce potent inflammatory responses in naive CD4+ T cells.
Steady-state dendritic cells (DCs) migrating in the lymph from the intestine induce tolerance to harmless intestinal antigens, preventing inflammatory responses. To determine if such DCs are inherently tolerogenic we collected intestinal lymph DCs (L-DCs) by cannulation of the thoracic duct of rats after mesenteric lymphadenectomy, and examined their capacity to activate naive CD4+ lymphocytes in an allogeneic mixed leucocyte reaction. L-DCs stimulated strong proliferative responses, induced secretion of inflammatory cytokines including interferon-gamma, and induced FoxP3-positive lymphocytes to divide. To determine if the activated CD4+ T cells had been tolerized, they were rested and restimulated with irradiated splenocytes. The restimulated CD4+ T cells again proliferated and secreted inflammatory cytokines. These data demonstrate that the DCs, which migrate from the intestine in the steady state, are paradoxically able to induce strong inflammatory responses from naive T cells, despite their role in the maintenance of oral tolerance.
Milling
S W F
SW
Glasgow Biomedical Research Centre, University of Glasgow, University Place, Glasgow, UK. s.milling@clinmed.gla.ac.uk
Jenkins
C D
CD
Yrlid
U
U
Cerovic
V
V
Edmond
H
H
McDonald
V
V
Nassar
M
M
Macpherson
G
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008196:Lymph / Q000276:immunology*; D008197:Lymph Node Excision / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000276:immunology / Q000601:surgery; D051381:Rats; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D007371:Interferon-gamma