INDUCTION OF TOLERANCE BY PARABIOSIS 335 



disposed of by the tolerant animals; no graft has in fact been 

 rejected before the loth postoperative day, which approximately 

 represents normal mean survival time of AG A grafts in Y59 

 hosts. A similar "lag" has also been observed in Y59 and W 

 recipients suffering from "parabiotic disease" and challenged 

 with Wistar skin grafts (Nakic and Silobrcic, 1962). A subnormal 

 immune response by the homologous radiation chimeras to skin 

 grafts from a strain not involved in the chimeric constitution has 

 been reported by Doak and KoUer (1961) and to sheep red blood 

 cells by Doria and co-workers (1962). Tliis phenomenon is 

 similar to that already reported by Billingham and Brent 

 (1959) regarding the impairment of a tolerant mouse's ability 

 to reject skin homografts from a strain unrelated to either 

 donor or recipient. A possible explanation is given elsewhere 

 (Nakic, 1962). 



The immune status of Y59 parabionts following 

 breakdown of tolerance 



In order to determine the immune status of tolerant parabionts 

 following breakdown of tolerance, ten such parabionts received 

 test grafts from parabiotic partners three to four weeks after com- 

 plete destruction of cross-graft(s). The results summarized in 

 Table III show that following low-degree tolerance the animal 

 remains in the state of heightened resistance and the next graft 

 from the parabiotic partners is rejected as a "white graft". 

 Parabionts which disposed of their grafts during the fourth post- 

 operative week or later behave differently. In these, the break- 

 down of tolerance is followed by a "nuU period" lasting several 

 weeks during which the formerly tolerant animal disposes of the 

 second graft from the parabiotic partner by the first-set reaction. 

 Even the third cross-graft placed two weeks after rejection of the 

 second cross-graft may fail to evoke a typical immune reaction 

 ("white graft"). 



