DISCUSSION 383 



whenever a certain threshold dose of lymphoid cells is exceeded in the 

 original inoculum. 



Billingham: That is certainly true of rats injected with thoracic duct 

 cells or lymph node cells. Above a certain threshold dose the clinical 

 events are remarkably constant. 



Nakic: I would like to make a point about the inactivation of donor 

 cells, or as some might call it, "allergic death" of donor cells. 



As Dr. Russell pointed out, there is something strange about it. One 

 lethaUy irradiates an animal and injects it with homologous bone 

 marrow. For a time the functional presence of donor cells is evident 

 only in their beneficial effect on the survival of the irradiated host. But 

 several months later, these same donor cells "turn wicked" and cause 

 fatal secondary disease. One would think that they have just been 

 gathering momentum for an all-out offensive against the host. 



We have had a similar experience in our experimental model. Con- 

 sider a separated parabiont dying of "parabiotic disease". Here donor 

 cells, despite the fact that they are in contact with an immense quantity 

 of antigen, not only do not succumb to "allergic death", but are quite 

 capable of killing the host. One would expect that in such a situation, 

 the whole of the donor cell population would be engaged in the offen- 

 sive, but it is not so ; if such a sick parabiont had also been challenged 

 with a skin graft from the third strain, donor cells would have a suffi- 

 cient reserve force to deal with this graft too. 



I would also like to add a few words regarding the relationship of 

 runting to tolerance : I believe that runts are tolerant animals — at least 

 no one has ever shown that they are not. Chronic runts are tolerant 

 animals, and all animals dying of "secondary disease" and "parabiotic 

 disease" are tolerant animals. Going back to Dr. Hildemann's paper, I 

 would think that, despite his contention to the contrary, he did induce 

 tolerance by the use of small lymphoid cells simply by inducing fatal 

 runting. 



