Induction of oral tolerance in TGF-beta 1 null mice.
Previous studies have suggested that oral tolerance induction by low doses of Ag is mediated by inhibitory cytokines, particularly TGF-beta 1. To examine the roles of TGF-beta 1 and other inhibitory cytokines in the induction of oral tolerance, TGF-beta 1 null mice and controls were gavaged with 10 to 20 mg (high dose) or 1 mg (low dose) of OVA for 3 days. After immunization with OVA, the in vitro proliferative response of OVA-specific popliteal lymph node cells was assessed. Lymphocytes from all TGF-beta 1 null mice fed high doses of OVA exhibited highly significant suppression compared with controls. A weaker, but still significant, suppression was observed in lymphocytes from the majority of TGF-beta 1 null mice fed low doses of OVA. In addition, supernatants from these lymphocytes exhibited lower levels of IL-4, IL-10, and IFN-gamma than those from water-fed control animals. These results indicate that while TGF-beta 1 may play a role in suppression, inhibitory cytokines are not the exclusive mechanism by which low dose oral tolerance is induced.
Barone
K S
KS
Department of Biology, Thomas More College, Crestview Hills, KY 41017, USA.
Tolarova
D D
DD
Ormsby
I
I
Doetschman
T
T
Michael
J G
JG
D000284:Administration, Oral; D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics*
D018845:CD11 Antigens; D007106:Immune Sera; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin