DISCUSSION 381 



Russell: As far as the effect of serum is concerned, these differences 

 are entirely a mystery to me. I didn't expect it to be as effective and, as 

 I said, we didn't get success with it in early experiments. I plan to go on 

 and try the effect of antiserum in abolishing tolerance in C57 mice in- 

 duced by Fj hybrid cells between DBA and C57. It might also be 

 worth while to see if we can abolish the tolerance we achieve to homo- 

 zygous DBA/i tissues using amethopterin. 



Medawar: Your doses of serum are enormous, aren't they ? — about 

 5 per cent of the body weight. 



Russell: They are. 



Breut: I wonder whether amethopterin would have an effect on 

 runting produced by presensitized cells. Perhaps the cells which are 

 undergoing the process of sensitization are particularly susceptible to 

 the drug and are knocked out as they are being sensitized. If this is true 

 you would abolish the runting effect and leave in the host only cells 

 which had not been stimulated by the antigens. There must be a lot of 

 cells in lymphoid tissue which do not react immunologically, and these 

 would continue the tolerance-inducing stimulus ; this explains the fact 

 that quite a few of your survivors were tolerant though they didn't 

 show the runting syndrome. 



Russell: Your thinking is very similar to my own, and this suggestion 

 is certainly very worth while; I haven't done such an experiment as yet. 

 Another one along similar lines would be to treat the donor animal 

 with the drug before using it as a donor. 



Voisin: Do you know anything about the selective effects of either 

 the drug or irradiation on the immunologically competent cell popu- 

 lation ? What are the cells which are the most readily destroyed or im- 

 paired and is there any known order of action ? 



Russell: I cannot answer this. I would be very interested to know an 

 answer. 



Mitcliison: I don't see the discrepancy between Dr. Brent's and Dr. 

 Russell's results with antiserum. May not the antibody, so to speak, 

 shoot down the missiles after they have already left the launching site ? 

 If Dr. Russell is agglutinating lymphocytes in the circulation, this might 

 procure a protective effect long after tolerance has been achieved. 



Brent: Presumably you have tested your animals for the presence of 

 donor cells after treatment with antiserum ? 



