Mechanism of induction of immunological tolerance. IV. The effects of ultra-low doses of flagellin

Abstract

Minute amounts of Salmonella adelaide flagellin were shown to be capable of inducing tolerance in newborn Wistar rats. With the range of doses, 10^-9–10^-1 μg, the following results were obtained:

(1) Tolerance could be induced in two zones of dosage by daily injections of flagellin during the first 2 weeks of life. The low zone corresponded to a dose of 10^-7 μg/g body weight and the high zone to 10^-3 μg/g body weight. Doses between these evoked an immune response.

(2) Daily injections of flagellin for 6 weeks resulted in a shift in the dosage required for low zone tolerance from 10^-7 μg/g body weight to 10^-5 μg/g body weight.

(3) The events of low zone tolerance occurred at an antigen concentration, which, in an organ such as the spleen of a newborn rat, never exceeded about 10^-14 M. The high zone of tolerance corresponded to an antigen concentration of about 10^-10 M.