VI 



IMMUNOLOGICAL TOLERANCE AND 

 RELATED PHENOMENA 



I . Homograft immunity and tolerance 



A summary has already been given of the work on the 

 antenatal induction of tolerance in mice by Medawar's 

 group. Taken along with the findings in natural chimaeras 

 resulting from twin pregnancies in cattle, sheep and, rarely, 

 in man, it is now possible to state that foreign cells implanted 

 before a certain critical stage in prenatal development can 

 survive without provoking the normal immune response and 

 will render the animal tolerant to a skin graft from the 

 strain supplying the foreign cells (Billingham, Brent and 

 Medawar, 1956^). Recent work, however, is developing 

 a keener interest in the necessity for mutual development of 

 tolerance between host and graft (Brent and Billingham, 

 1957). Many of the animals rendered tolerant by the 

 inoculation of spleen cells of a foreign strain showed a marked 

 atrophy of lymphoid tissue, loss of weight, low-grade diar- 

 rhoea and eventual death. The interpretation is presumably 

 that the implanted splenic cells include many representatives 

 of antibody-producing clones, some of which are stimulated 

 to produce antibody against host components which are not 

 represented in the graft. To obtain the desired experimental 

 result in which the experimental animals remain healthy 

 and tolerant of the graft, a mutual tolerance must be 

 established. The mechanism of graft tolerance of the host 

 has yet to be worked out. 



It is already clear that the nature of the strains of mice 

 concerned is vitally important. Billingham (1958), for in- 

 stance, finds that when A strain mice are intravenously 

 inoculated on the first day of fife with cells from strain CBA, 



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