406 GENERAL DISCUSSION 



that graft-versus-host reactions can be a contributory factor. I 

 think Castermans' experiments show that very clearly. He re- 

 peatedly injected large numbers of immunologically competent 

 cells into adult animals, and they eventually overruled the host 

 response and, by reacting against the host antigens, brought about 

 the death of the animals. What is more, animals in this state 

 turned out to be tolerant of the donor antigens. This point seems 

 to be clearly an example of host depletion or debilitation. 



Hildemann: Perhaps the best example of full tolerance without 

 graft-versus-host reactions derives from Nature's regular experi- 

 ment in natural parabiosis with multiple non-identical embryos in 

 cattle and sheep. Here we find a long-term exchange of cells 

 between animals in utero. The resulting chimerism and tolerance 

 usually persist indefmitely in postnatal life and so far as I know 

 there is no evidence that these animals suffer any immunological 

 impairment whatsoever. 



Nakic: I gathered from Dr. Brent and from Dr. Hasek that they 

 did not analyse histologically the spleens or lymph nodes of stable 

 tolerant chimeras so we still don't know whether or not lymphoid 

 organs of these animals show any differences from the normal. 



I would like to go back to Dr. Brent's point about using em- 

 bryonic cells to induce tolerance in embryos. I agree that in 

 several strain combinations tolerance induced with embryonic cells 

 is not accompanied by overt signs of graft-versus-host reaction. 

 This is used as a proof that donor cells being embryonic are capable 

 of acquiring tolerance and are therefore incapable of reacting 

 against the host. 



I have, however, quite a different explanation for this pheno- 

 menon : it has been shown by several workers (Cock and Simonsen 

 in chickens, Billingham and Brent in mice) that it is very difficult 

 to induce fatal run ting in animals older than 20 days ; we have had 

 a similar experience with rats. Incidence of fatal runting is very 

 low even in mice 10 days old. I think that embryonic donor cells 

 have to mature before they become capable of reacting against the 



