Macrophages pulsed with sterol‐conjugated benzylpenicilloylated eicosa‐lysine induce T cell‐mediated suppression of IgE antibody formation in mice

摘要

AbstractThe conjugation of two lipophilic p‐oxymethylbenzyl‐3β‐cholestanylsuccinate groups to fully benzylpenicilloylated eicosa‐L‐lysine BP20Lys20(OSuco)2 greatly potentiated its ability to suppress anti‐BPO IgE antibody formationin vivoin mice. This enhanced tolerogenicity was due to the ability of BPO20Lys20(OSuco)2to induce T suppressor cells (Luescher, I. F. et al.,Eur. J. Immunol.1984.14:68). In the present study the role of adherent cells in the induction of T suppressor cells by BPO20Lys20(OSuco)2was investigated. Low numbers of macrophages pulsedin vitrowith BPO20Lys20(OSuco)2, but not with the hydrophilic analog BP020Lys20‐OH, suppressed anti‐BPO IgE antibody formation upon transfer into syngeneic recipients. This suppression was antigen and IgE specific, and was manifested in naive as well as in previously immunized mice. By cell transfer experiments it was found that the suppression was sensitive to cyclophosphamide. The IgE suppression was not due to carry‐over of BPO20Lys20(OSuco)2by the transferred macrophages since the amount of cell‐associated antigen was approximately 500‐fold too low to account for the observed suppressions.The capability of BPO20Lys20(OSuco)2to elicit anaphylaxis in passively sensitized rats was significantly lower in comparison to the hydrophilic analog BPO21Lys20OH. Adherent cells pulsed with BPO20Lys20(OSuco)2, although strongly suppressing IgE antibody formation, failed to elicit any detectable anaphylaxis. The role of adherent cells in the induction of T cell‐mediated suppression of IgE antibody formation by lipid‐modified antigens is discussed and novel therapeutical concepts to achieve desensitization of drug allergic