The introduction of one or two 3 beta-cholestanyl residues into benzylpenicilloyl-eicosa-L-lysines greatly potentiates their tolerogenicity for anti-benzylpenicillol IgE antibody formation.
BALB/c mice were repeatedly immunized with microgram doses of benzylpenicilloylated Ascaris protein(s) (BPO9Asc) in alum. At different stages of the immune response, BPO21 eicosa-L-lysine or two analogs containing one or two hydrophobic p-oxymethylbenzyl-3 beta-cholestanyl succinate (OSuco) groups were injected. When injected early in the immune response, the anti-BPO IgE antibody formation was much more strongly and permanently suppressed by the lipophilic conjugates than by the hydrophilic BPO21 eicosa-L-lysine. A similar, but less marked, suppressive effect was observed on the anti-BPO IgG1 response. By adoptive cell transfer experiments, it was found that the OSuco-containing derivatives induce and act via suppressor T lymphocytes, since this cell-mediated suppression was sensitive to cyclophosphamide or to treatment with anti-Lyt-2.2 antibody plus complement. When these compounds were injected into repeatedly immunized mice producing late ongoing antibody responses no differences in suppression between hydrophilic and hydrophobic derivatives were observed. In this case, the IgE response was suppressed by about 50%, while the IgG1 response was not affected. These results are compatible with the suggestion that early IgE responses are most sensitive to T cell-mediated suppression and that T suppressor cells are better induced by lipophilic than by hydrophilic antigens. The late ongoing IgE response, on the other hand, is less amenable to T cell-induced suppression and tolerogenic effects brought about by plurivalent BPO antigens operate directly on hapten-specific IgE-bearing B cells, regardless of their lipophilic character.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D044482:Benzeneacetamides; D002776:Cholestanes / Q000276:immunology; D004083:Cholestanol / Q000494:pharmacology*; D002784:Cholesterol / Q000031:analogs & derivatives*; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010400:Penicillin G / Q000031:analogs & derivatives / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D013723:Teratogens
D044482:Benzeneacetamides; D002776:Cholestanes; D007074:Immunoglobulin G; D013723:Teratogens; C015026:benzylpenicilloyl G; D007073:Immunoglobulin E; D004083:Cholestanol; D003520:Cyclophosphamide; D002784:Cholesterol; D010400:Penicillin G