GENERAL DISCUSSION 407 



host; the same is true of embryonic host cells. The maturation 

 process may take 1-2 weeks, and by this time the host may be well 

 out of the danger period. 



Billingham: In our earher work Dr. Brent and I did find it very 

 difficult to destroy tolerant mice immunologically by inoculation 

 with donor-strain lymphoid cells. High dosages of homologous 

 spleen cells were ineffective. But Dr. Silvers and I have looked 

 into this again, using either F^ hybrid genetically tolerant adult 

 mice or immunologically tolerant mice. With the CBA and A 

 combinations if you use as few as about 50 or 100 million regional 

 node cells, then it is not difficult to kill these mice quite promptly. 

 In other words, what spleen cells will do to a newborn mouse, 

 adult node cells seem to do fairly well, in relatively low dosage, to 

 adult mice. I think this is something to take into consideration. 



Voisin: It seems clear to me that in some cases replacement has 

 something to do with the establishment of tolerance, and I have 

 been sympathetic to this concept for several years. However, one 

 is obliged to recognize that there are some discrepancies between 

 this concept and some observations on tolerance. On the other 

 hand, we all know that there are a few discrepancies with the 

 classical concepts of immunological tolerance — they are not very 

 numerous, but I think they are highly significant. The only way I 

 can think of to reconcile the two views is to think in terms of 

 immunological enhancement. I feel strongly that most of the 

 discrepancies which are observed either in the replacement theory 

 or in the classical views on immunological tolerance to Hving cells 

 can be explained on the basis of a reciprocal double-headed re- 

 action between the host and the injected cells when these are 

 immunologically competent — the double-headed reaction being, 

 as I said this morning, due to serum antibodies on the one hand, 

 leading to enhancement (or, at a higher titre, to cytotoxic activity) ; 

 and, on the other hand, to cellular reactivity, more or less of the 

 type of delayed hypersensitivity. I think that with slight modifi- 

 cations and adaptations (which might concern mainly selective 



