MODIFICATION OF RUNT DISEASE 373 



of the ultimate survivors shov^ed slight temporary signs of dis- 

 ability, most grew at very nearly a normal rate to become quite 

 normal in outv^ard appearance except for the loss of pigmentation 

 previously mentioned (Fig. 15). A fev^ trials of single doses of 

 0-75 mg. on the day of birth shortly after cell injection proved 

 ineffective. When grafted at six to seven v^eeks of age, 54 per cent 

 of these surviving animals v^ere found to be highly tolerant of 

 DBA/ 1 skin grafts (i.e. survival for more than 30 days) some of 

 v^hich have been observed as long as 95 days (Fig. 16). Three of 

 these tolerant animals w^ere also grafted v^ith skin from A-strain 

 donors and in each case these grafts were fully rejected by the 

 eleventh day. Four other animals, bearing long-term homografts 

 of DBA/ 1 skin, were killed and their spleens and lymph nodes 

 transferred as cell suspensions to individual normal adult C57BL/6 

 mice by intraperitoneal injection. DBA/i skin grafts applied 

 five days thereafter as a "chimera test" according to the design 

 of Mitcliison (1956) were fully destroyed in seven to eight days 

 confirming that the original tolerance-conferring inoculum, or at 

 least some of its descendent cells, had survived. Doses smaller than 

 0-037 mg./kg. have not so far been used. 



IV. Secondary transfer of cells from runts 



Our preliminary efforts to transfer runt disease by injecting 

 spleen cell suspensions from animals with the disease into newborn 

 recipients of the same strain can be summarized as follows. A 

 total of 18 recipients have so far received injections of pooled 

 spleen cells from runts in their sixth or seventh days of life. Each 

 received from 12 to 32 million nucleated cells intravenously. In 

 no case has any distinct retardation of development in the 

 injected animals been observed. 



Injection of a portion of the cell suspensions used in these 

 experiments into adult C57BL/6 recipients results in subsequent 

 accelerated rejection of DBA/ 1 skin grafts, thus demonstrating 

 the presence of DBA/ 1 antigens. When they have reached an 



TRANS. — 13 



