268 DISCUSSION 



million cells of F^ hybrid spleen, doses of less than 5 million C57BL spleen 

 cells were sufficient to give a practically 100 per cent kill. This seems to 

 suggest that you can get lethal runting under circumstances where you 

 have by no means full, or even detectable tolerance, in this particular 

 system. 



Nakic: I would like to protest against the use of the term "Hver cells" 

 when what is meant is hver parenchyma cells. Liver cell suspension 

 contains many immunologically competent cells, but I do not believe 

 that tolerance can be induced with liver parenchyma cells. 



Hildemann: The point here is that foetal hver cells will become 

 tolerant of the newborn host and vice versa, so you have reciprocal 

 tolerance. This approach has been much used by radiation immuno- 

 geneticists in the repair of radiation injury. It is true that foetal liver is a 

 heterogeneous population of cells, and we did this to estabhsh the point 

 that it is possible to make newborn A-lines tolerant of C57 cells in 

 general, but apparently not with C57 small lymphocytes derived from 

 peripheral blood — at least over the dosage range that we have thus 

 far tested. 



Brent: I certainly would strongly support the idea that A-hne mice 

 can be made tolerant of C57 antigens. Billingham and I found that if 

 newborn A-line mice were injected with roughly 5 milHon bone 

 marrow cells it was possible to induce tolerance to C57 skin grafts. 



Hildemann: We retested this finding because our hnes are probably 

 not isogenic with yours, so it was desirable to estabhsh the point once 

 again. 



Brent: The point I would like to make is that in my very limited 

 experience of cytotoxic tests, which I carried out with the aid of such 

 experts as Dr. Batchelor and Dr. Silverman, it doesn't seem to be a very 

 good technique for detecting rather small numbers of cells. In my own 

 experiments the number of donor cells in the chimeras is relatively 

 small; it might be something of the order of i to 5 per cent. I doubt 

 that the cytotoxic test can reveal the presence of such a low proportion 

 of cells. It might be more useful to try Mitchison's test for donor cells 

 — to see whether there are enough donor cells to sensitize normal mice 

 against skin grafts from the donor strain. Such a test can be made to be 

 reasonably quantitative. It might also be helpful to skin graft all your 

 animals in order to reveal how many of them have become tolerant. 



