Suppression of hen egg lysozyme-induced arthritis by intravenous antigen administration: no role in this for antigen-driven bystander suppression

Abstract

SUMMARYThe induction of tolerance, particularly by intervention before established immunity, is widely accepted. We studied the effects of intravenous (i.v.) administration of hen egg lysozyme (HEL). before as well as after immunization, on a HEL-induced arthritis. Arthritis and also cartilage destruction were almost completely suppressed when 100 ^i% HEL was injected before immunization. Antigen-specific proliferative T cell responses and IL-2 production in vitro were inhibited. Antigenspecific immunogiobulin and IgGl titres were equal in control and tolerized mice, in contrast to lowered IgG2a litres in tolerized animals. Detailed hisiological studies showed that the immune complex-dependent poiymorphonuclear 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 tolerized mice. I.V. administration of 100 ^g HEL after immunization could only marginally reduce infiltrate and exudate. and no reduction of cartilage destruction was seen. An elegant way to interfere in an established 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 not reduce a methylated bovine serum albumin (BSA)-arthritis. We conclude that arthritis can be suppressed almost totally when HEL is injected intravenously before immunization. Treatment after immunization is less efTeciivc. The i.v. induced suppression is T cell-mediated and antigen-specific: no bystander suppression circuit can be generated.Keywords tolerance intravenous arthritis antigen-specific antigen-driven bystander suppression