Active suppression in orally tolerized rats coincides with in situ transforming growth factor-beta (TGF-beta) expression in the draining lymph nodes.
Adult rats were fed pellets containing ovalbumin (OvA) during 4 weeks, and were 2 weeks thereafter immunized subcutaneously with a mixture of OvA and human serum albumin (HSA) in Freund's complete adjuvant (day 0). As a result of the immunization, the draining lymph nodes of the nontolerized (control) rats were heavily enlarged from day 10 to day 18; however, this size increase was absent in the OvA-fed rats. This manifestation of active suppression in the tolerized rats was preceded by the appearance of scattered CD4+ TGF-beta-expressing T cells in the T cell area of their lymph nodes (days 5-8); correspondingly, the levels of TGF-beta mRNA in the nodes were elevated in the tolerant rats compared with the control rats. The anti-OvA antibody levels in sera from the rats revealed that there was an initial B cell priming in the OvA-fed group, with levels higher than in the control group during the first week. Thereafter, suppression governed the response, and from day 10 onwards the anti-OvA levels were considerably lower than in the controls. When other groups of animals were pretreated with neutralizing anti-TGF-beta antibodies 1 day before the immunization, the anti-OvA response of the OvA-fed rats was restored to the levels of the control group, demonstrating the importance of TGF-beta in the maintenance of suppression. In conclusion, we demonstrate that TGF-beta-producing cells appear in the draining lymph nodes shortly after immunization in rats made orally tolerant using a relatively high-dose feeding regime; these cells are probably responsible for the down-regulation of the immune response observed in the OvA-fed rats.
Lundin
B S
BS
Department of Clinical Immunology, Göteborg University, Sweden. samuel.lundin@microbio.gu.se
Karlsson
M R
MR
Svensson
L A
LA
Hanson
L A
LA
Dahlgren
U I
UI
Telemo
E
E
D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004435:Eating / Q000276:immunology*; D006614:Hindlimb / Q000276:immunology; D007108:Immune Tolerance; D007114:Immunization; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000008:administration & dosage / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; D010047:Ovalbumin