MODIFICATION OF RUNT DISEASE 



359 



sacrificed. There is no evidence that very small doses allow the 

 establishment of tolerance without the damaging effects of a 

 graft-against-host reaction. 



Doses in excess of 5 million cells have little influence in hastening 

 the onset of the disease or of death, suggesting a dosage threshold. 



9 r 



2 survive 



10 12 14 16 18 20 22 24 26 28 30 



DAYS OFAGE 



Fig. 8. Dosage of DBA/i spleen cells. Mean weight-gain 

 curves of four litters of C57BL/6 mice treated with different 

 doses of DBA/ 1 spleen cells intravenously on the day of 

 birth. Numbers in parentheses indicate the number of 

 animals in each Htter. Up to a dosage of about 5 milHon 

 cells the rate of onset of disease and its severity appear to 

 increase slightly. Above this dosage level little increase in 

 potency of the inoculum is observed. 



In all later experiments doses well above this threshold were 

 accordingly used for consistency. 



In contrast to the reliability of the intravenous route the 

 subcutaneous and intraperitoneal routes are much less dependable, 

 as Billingham and Brent (1959) found. Of twelve animals 

 injected intraperitoneally with about 15 million foreign spleen 

 cells only a single one died. This animal did, however, have all 



