GENERAL DISCUSSION 405 



Unfortunately we do not have any measure of the reactivity on 

 the part of the graft against the host required to get an expression 

 of tolerance. 



Woodruff: I agree. But I think it is worth making the point that 

 graft-against-host reaction per se can weaken immunological re- 

 activity. Howard and I (Howard, J. G. and Woodruff, M. F. A. 

 [1961]. Proc. roy. Soc. B., 154, 532) reported some work on this last 

 year in which graft-against-host disease was induced by injecting 

 parent-line spleen cells into F^'s without any radiation and where 

 one could demonstrate impaired reactivity both towards skin 

 grafts and a salmonella antigen. One of our two parent strains 

 produced severe, and the other relatively mild, graft-versus-host 

 disease in the hybrid, and the general impairment of immunolo- 

 gical reactivity corresponded more or less to the severity of the 

 symptoms of graft-versus-host disease. So while I would agree that 

 tolerance can occur without any element of graft-versus-host re- 

 action, I can imagine situations in which this additional factor 

 might tip the scales as to whether you are going to get tolerance 

 or not. 



Simonsen: I would Hke to add one more case to Dr. Brent's list 

 of arguments — a point which I think is particularly pertinent to 

 Dr. Nakic's experiments — the fact that tolerance can be induced in 

 adult parental strains parabiosed with F^ hybrids, in which case the 

 animal to become tolerant is not subject to graft-versus-host 

 reaction. I would like to know. Dr. Nakic, if you think com- 

 petitive replacement also occurs in these animals, and if you have 

 any evidence of it. 



Nakic: I have no experience with Fj hybrid cells. I want to 

 point out, however, that in contrast to dead antigen, these cells 

 are living, self-replicating units capable of absorbing a lot of anti- 

 body. Recently Cudkowitz from Oak Ridge reported that at 

 least in some strain combinations, Fj hybrid spleen cells could be 

 capable of reacting immunologically against parental tissue. 



Brent: With regard to Prof Woodruff's point, I certainly agree 



TRANS. — 14 



