382 DISCUSSION 



Russell: Yes, but only by skin graft tests for tolerance, which may 

 have missed some persisting cells. 



Brent: It would be interesting to know whether or not you are 

 actually eliminating the donor cells or whether you are simply reducing 

 the cell population to a permissible level. 



Russell: Exactly. I think that is something we must try to find out 

 about. 



Hasek: Have you tried to aboHsh tolerance by using serum antibodies 

 that are concentrated — for example, y-globulin concentrated on DEAE 

 cellulose or by some other concentration technique ? 



Russell: I haven't tried this yet. 



Hasek: We can abolish tolerance in heterologous systems using large 

 doses of serum. These sera destroy cellular chimerism in tolerant 

 animals and lead to the destruction of tolerated skin grafts. Both the 

 cytotoxic components and heteroprecipitins take part in the reaction; 

 the latter are responsible for the early vascular-necrotic changes in the 

 graft. If we use y-globulin instead of the large quantity of serum, it 

 also works well (HaSek, M. [1962]. Folia biol (Prague), 8, 57). Thus 

 I feel that it would be worth while trying once again the effect 

 of serum antibodies in the homologous systems using concentrated 

 antibodies. 



Hildemami: If each competent lymphoid cell injected is capable of 

 producing a certain quantum of damage in the neonatal host, it would 

 seem surprising that normal lymphoid cells at varying doses should not 

 give different median survival times. If I understand Dr. Russell 

 correctly, he obtained the same median survival times as we did with 

 small lymphocytes over a comparatively wide dosage range. However, 

 when preimmunized lymphocytes are injected then accelerated death 

 follows. Is this perhaps because the normal lymphocytes carry a semi- 

 automatic rifle and the immune ones a machine gun ? Or does this relate 

 to the number of competent replicating cells present and therefore the 

 intensification of the attack ? The dosage relationships are not as clear- 

 cut as one might expect. As I recall the results of BiUingham and coll- 

 eagues with rats, though they gave no median survival times, the time 

 distribution of runt disease in the rat appears to be very similar to that 

 in mice, that is median survival times around 16-17 days. So it would 

 appear that the time course of events leading to death is much the same 



