242 HILDEMANN, LINSCOTT AND MORLINO 



the blood. However, all the evidence from the present series of 

 studies is against this possibihty. 



Transplantation disease as a function of cell dosage 



Our initial experiments were directed toward ascertaining the 

 dosage of C57BL/6 peripheral blood lymphocytes required to 

 procure runt disease in newborn A/Jax mice. These results are 

 summarized in Table I. Lymphocyte doses of 200,000 and 750,000 

 cells failed to induce any discernible graft-versus-host reactions. 

 The injected animals developed quite normally. When 800,000- 

 900,000 cells were inoculated by the intracardiac route on the day 

 of birth, however, symptoms of runt disease were subsequently 

 apparent in 12/19 animals with two deaths ensuing. Further 

 experiments revealed that about 800,000 cells constituted a 

 threshold dose of small lymphocytes for the induction of runt 

 disease in this strain combination. Injections of 0-9-1 '5 million 

 small lymphocytes produced a high incidence of lethal trans- 

 plantation disease. Over this dosage range, there was no sub- 

 stantial difference in the severity of the disease syndrome. Ninety- 

 six of a total of III injected mice were affected with symptoms 

 varying from failure to gain weight at the normal rate, with even- 

 tual recovery, to death following profound systemic disease. In 

 this group 66/11 1 animals or 59* 5 per cent succumbed. The time 

 distribution of deaths in this series is plotted in Fig. 2. It will be 

 noted that the earliest death occurred at nine days and only one 

 animal survived beyond 30 days. This represents a normal time- 

 mortality distribution with a median survival time (MST) of 

 16-4 (15 -4-1 7 -5) days within 95 per cent confidence limits. If 

 the data are considered as a truncated distribution with n = iii, 

 taking into account also the animals which failed to die within 

 70 days, a median survival time of 21*2 (19- 5-23 '2) days is 

 obtained. For reasons to be considered below, the MST of 16-4 

 days is probably a better quantitative approximation. Animals 

 dying or cannibalized within five days after injection were 



