RT Journal Article
SR Electronic
T1 Expanding Dendritic Cells In Vivo Enhances the Induction of Oral Tolerance
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 5815
OP 5825
VO 160
IS 12
A1 Viney, Joanne L.
A1 Mowat, Allan M.
A1 O’Malley, Jamie M.
A1 Williamson, Eilidh
A1 Fanger, Neil A.
YR 1998
UL http://www.jimmunol.org/content/160/12/5815.abstract
AB The intestine is under perpetual challenge from both pathogens and essential nutrients, yet the mucosal immune system is able to discriminate effectively between harmful and innocuous Ags. It is likely that this selective immunoregulation is dependent on the nature of the APC at sites where gut Ags are processed and presented. Dendritic cells (DC) are considered the most potent of APC and are renowned for their immunostimulatory role in the initiation of immune responses. To investigate the role of DC in regulating the homeostatic balance between mucosal immunity and tolerance, we treated mice with Flt3 ligand (Flt3L), a growth factor that expands DC in vivo, and assessed subsequent systemic immune responsiveness using mouse models of oral tolerance. Surprisingly, mice treated with Flt3L to expand DC exhibited more profound systemic tolerance after they were fed soluble Ag. Most notably, tolerance could be induced in Flt3L-treated mice using very low doses of Ag that were ineffective in control animals. These findings contrast with the generally accepted view of DC as immunostimulatory APC and furthermore suggest a pivotal role for DC during the induction of tolerance following mucosal administration of Ag.