Aberrant tolerance induction with cationic antigens.
We studied the induction of tolerance in female C57B1/6 mice by oral and intravenous (i.v.) administration of protein antigens before immunization. Native proteins [chicken egg albumin (OVA), bovine serum albumin (BSA)] and their cationic derivatives [amidated (a)OVA, aBSA, methylated (m)BSA] were compared in their capacity to suppress cell-mediated immunity (CMI), as measured by a delayed type hypersensitivity test (DTH). Oral feeding of 0.5 mg negative proteins gave a clear suppression. By contrast, cationic derivatives (50 micrograms to 50 mg) did not suppress CMI. Data from cross-experiments, where aOVA was fed in OVA-immune mice, showed no suppression at all. When OVA was fed in aOVA-immune mice, only a partial suppression was achieved. The potency to induce tolerance differed also when the antigens were administered i.v.: 25 micrograms OVA was sufficient to induce a clear suppression, whereas a much higher amount of aOVA (500 micrograms) caused marginal suppression in OVA- and aOVA-immune mice, respectively. Nevertheless, when concentrations of aOVA up to 2.5 mg were tested in a chronic model of arthritis, a significant suppression was achieved. The differences in inducing a CMI suppression may have implications for the feasibility of immunointervention. Successful modulation of human arthritis may be highly dependent on the nature of the antigen involved.
Jacobs
M J
MJ
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
van den Hoek
A E
AE
van de Putte
L B
LB
van den Berg
W B
WB
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology*; D002412:Cations; D005260:Female; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D007114:Immunization; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology
D000941:Antigens; D002412:Cations; D012710:Serum Albumin, Bovine; D010047:Ovalbumin