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 resul t of the immunization, the draining lymph nodes of the non-tolerized (contr ol) rats were heavily enlarged from day 10 to day 18; however, this size in crease was absent in the OvA-fed rats. This manifestation of active suppres sion 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 (day s 5-8); correspondingly, the levels of TGF-beta mRNA in the nodes were elev ated in the tolerant rats compared with the control rats. The anti-OvA anti body 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 a nti-TGF-beta antibodies 1 day before the immunization, the anti-OvA respons e of the OvA-fed rats was restored to the levels of the control group, demo nstrating the importance of TGF-beta in the maintenance of suppression. In conclusion, we demonstrate that TGF-beta-producing cells appear in the drai ning lymph nodes shortly after immunization in rats made orally tolerant us ing a relatively high-dose feeding regime; these cells are probably respons ible for the down-regulation of the immune response observed in the OvA-fed rats.