Oral tolerance to haptens: intestinal epithelial cells from 2,4-dinitrochlorobenzene-fed mice inhibit hapten-specific T cell activation in vitro.
The mechanisms underlying the induction of immunological tolerance after feeding soluble exogenous antigens, including proteins and haptens, are still unclear. Using a model of oral tolerance to the contact-sensitizing hapten 2,4-dinitrochlorobenzene (DNCB), we have compared the ability-of intestinal epithelial cells and of Peyer's patch APC to present DNCB in vitro or ex vivo after oral feeding, to specific peripheral lymph node T cells from DNCB-sensitized mice. In contrast to Peyer's patch APC, which induce efficient hapten-specific T cell activation upon exposure to the hapten either in vitro or in vivo, mature MHC class-II-positive intestinal epithelial cells were unable to induce T cell activation in either case. Interestingly, enterocytes from DNCB-fed mice exerted a dramatic inhibitory effect on the proliferative response of hapten-primed T cells in response to dinitrobenzene sulfonate presented by syngeneic spleen cells. This inhibitory effect, which was also observed with supernatant of intestinal epithelial cells from DNCB-fed mice, could be reversed by neutralizing anti-transforming growth factor (TGF)-beta antibodies. In addition, pre-incubation of hapten-sensitized T cells with enterocytes from DNCB-fed mice induced T cell anergy, which could be reversed by exogenous interleukin-2 or interleukin-4. These data demonstrate that intestinal epithelial cells activated in vivo by oral administration of DNCB are able to block proliferation of activated T cells through secretion of immunosuppressive cytokines such as TGF-beta. It is proposed that intestinal epithelial cells may play a significant role in oral tolerance by limiting T cell-mediated hypersensitivity responses.
Galliaerde
V
V
INSERM U404, Immunité et Vaccination, Institut Pasteur de Lyon, France.
Desvignes
C
C
Peyron
E
E
Kaiserlian
D
D
D000284:Administration, Oral; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000276:immunology; D004847:Epithelial Cells; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007114:Immunization; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000166:cytology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology
D017077:Culture Media, Conditioned; D004137:Dinitrochlorobenzene; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; C045305:2,4-dinitrofluorobenzene sulfonic acid; D015847:Interleukin-4; D004139:Dinitrofluorobenzene