On the induction of immunological tolerance to a self-reproducing antigen

Abstract

Inoculation of a dose of 1000 LD₅₀ of LCM virus intraperitoneally into newborn mice within the first 18 hours of life always resulted in the development of a complete and permanent state of tolerance to the virus as judged by a life-long viraemia with titres of [unk] 10^2.3 and complement fixation (CF) titres of <4.

Sixteen litters of outbred white Swiss mice were inoculated intraperitoneally with this virus dosage at an age of 2–9 days. A total of 103 babies were inoculated. Of these babies sixty survived the first 2 weeks of life. They were followed for 24 weeks with regard to the course of the viraemia and CF-antibody production.

On the basis of the values obtained in this manner in the individual mouse seven types of course could be distinguished. These represented the following immunological phenomena: (1) complete and permanent tolerance; (2) disappearance of the viraemia and antibody formation; (3) disappearance of the viraemia without antibody formation; (4) permanent viraemia with antibody formation; and (5) temporary, incomplete tolerance as illustrated both by temporary antibody formation with constant viraemia and by temporary viraemia elimination without antibody formation.

The results indicate that a dissociation of the immunological response of the mouse to LCM virus can take place, presumably representing a state of split tolerance. Furthermore the results indicate that specifically reactive cells can be present in an apparently completely tolerant animal. These findings are discussed in the light of the hypothesis that complete tolerance represents the maximum degree of specific immunosuppression.