Further Studies on the Effect of Specific Antiserum on Induction, Maintenance and Termination of Immunologic Tolerance

Abstract

Summary Establishment of immunologic tolerance to soluble somatic antigens derived from Shigella paradysenteriae was prevented in neonatal mice by a single injection of either rabbit or mouse antiserum to Shigella. Serum dilutions less than 1:100 were generally necessary to demonstrate this effect, even when the sera had agglutinin titers greater than 1:5120. Injection of antiserum on the day of birth, or 1 day thereafter, readily interfered with establishment of tolerance. An interval of several days or more between injection of antiserum and SSA resulted in no demonstrable effect on tolerance induction. γ-Globulin fractions derived either from rabbit or mouse antisera had similar effects in preventing tolerance induction. IgM and IgG rich fractions prepared by sucrose gradient centrifugation of γ-globulin prepared from pooled rabbit or mouse hyperimmune serum were also effective. However, IgG fractions prepared from “early” immune rabbit or mouse serum, which had low titers to Shigella, were ineffective. Whole serum, γ-globulin, or IgM and IgG fractions pooled from serum specimens obtained from partially tolerant mice several months old also had little or no effect when injected into other mice at birth, together with SSA. Undiluted “tolerant” sera, even those with titers in the range of 1:256, were less effective in blocking establishment of tolerance than higher dilutions of “early immune” mouse or rabbit serum with lower agglutinin titers. Injection of specific antiserum or immunoglobulin fractions generally did not affect established tolerance in young adult mice. However, injection of such serum to tolerant mice several months of age often resulted in more rapid termination of tolerance.