SUPPRESSION OF HEN EGG LYSOZYME-INDUCED ARTHRITIS BY INTRAVENOUS ANTIGEN ADMINISTRATION - NO ROLE IN THIS FOR ANTIGEN-DRIVEN BYSTANDER SUPPRESSION

The induction of tolerance, particularly by intervention before establ ished immunity, is widely accepted. We studied the effects of intraven ous (i.v.) administration of hen egg lysozyme (HEL), before as well as after immunization, on a HEL-induced arthritis. Arthritis and also ca rtilage destruction were almost completely suppressed when 100 mug HEL was injected before immunization. Antigen-specific proliferative T ce ll responses and IL-2 production in vitro were inhibited. Antigen-spec ific immunoglobulin and IgG1 titres were equal in control and tolerize d mice, in contrast to lowered IgG2a titres in tolerized animals. Deta iled histological studies showed that the immune complex-dependent pol ymorphonuclear cell phase (< 24 h after arthritis induction) was equal for control and HEL-injected mice. Only in the T cell-dependent phase of the arthritis (> 24 h), did suppression become pronounced in toler ized mice. I.V. administration of 100 mug HEL after immunization could only marginally reduce infiltrate and exudate, and no reduction of ca rtilage destruction was seen. An elegant way to interfere in an establ ished immunity can be offered by creation of bystander suppresson. We show that i.v. administration of HEL followed by triggering with HEL, at the moment either of immunization or of arthritis induction, does n ot reduce a methylated bovine serum albumin (BSA)-arthritis. We conclu de that arthritis can be suppressed almost totally when HEL is injecte d intravenously before immunization. Treatment after immunization is l ess effective. The i.v. induced suppression is T cell-mediated and ant igen-specific: no bystander suppression circuit can be generated.