INDUCTION OF TOLERANCE BY PARABIOSIS 339 



marrow of a tolerant female parabiont dying of "parabiotic 

 disease" 33 days following the operation. 



The cytological method may well be applicable in other 

 mammalian species, including man, and a similar method has 

 already been used in the chicken by Biggs and Payne (1959). 



Conclusions 



The availabihty of a strain combination in which the pheno- 

 menon of tolerance is not associated with clinically manifest 

 graft-versus-host reaction renders possible a more accurate 

 observation of the successive stages that lead to the establishment 

 of the state of specific tolerance in adult parabionts. 



The apparent paradox of tolerance following short-term 

 parabiosis is that the state of specific non-reactivity is induced in 

 an immunologically competent animal by a procedure that 

 primarily causes sensitization. In some parabionts the immune 

 reaction is of sufficient intensity as to cause destruction of the skin 

 homograft by the 12th postoperative day. In others, a more 

 lingering process may achieve the same result, that is total destruc- 

 tion of the cross-graft, by a series of successive immune crises. 

 In still others, the immune process becomes seemingly arrested 

 during the fourth postoperative week but not before the cross- 

 graft has been considerably reduced in size. In these animals the 

 next cross-graft is well accepted, sometimes throughout life. 



What then, is the mechanism by which an already sensitized 

 animal is subsequently rendered specifically unresponsive? We 

 had already suggested (Nakic et ah, 1961) that the basic factor 

 responsible for this phenomenon might be the difference in 

 immunological reactivity between the parabiotic partners. This 

 factor would determine the difference in rate and intensity by 

 which the process of immunization would proceed in either 

 parabiont despite the fact that both are antigenically stimulated 

 at the same time. The asymmetry in tolerance responsiveness 



