INDUCTION OF TOLERANCE BY PARABIOSIS 33I 



Brent in mice (1959). Older parabionts may display a high degree 

 of tolerance without fatal manifestations of "parabiotic disease". 

 Some hosts may show mild recurrent attacks of the disease 

 alternating with immune crises in the graft. 



The hypothesis of competitive replacement 



Based on the results described above, the competitive replace- 

 ment of the immune system of the host by that of the donor has 

 been proposed as a possible mechanism responsible for induction 

 of tolerance following short-term parabiosis between bilaterally 

 incompatible partners (Nakic et ah, 1961). The replacement 

 would take place as a result of transfer of immunologically 

 competent cells from one parabiont to another through vascular 

 anastomotic channels. The ensuing competition between actively 

 immunized cells of the host and the donor would damage the 

 lymphopoietic tissues of the host and cause non-specific depression 

 of the immune reaction. In combinations where antigenic 

 conditions favour a stronger unidirectional immunity reaction the 

 more reactive partner may, by an immunological vicious circle, 

 exterminate host lymphoid tissue and replace it with its own. 

 Specific tolerance would result, the immune system of the donor 

 "tolerating" grafts of donor type and reacting against any other 

 antigen. "Parabiotic disease" would thus be a manifestation of 

 the immunological attack of donor cells against the host. 



Induction of tolerance in Wistar->Y59 strain combination 



Our more recent work concerns another strain combination, 

 Wistar->Y59. Wistar rats were obtained from another Institute* 

 where inbreeding of this non-homogeneous stock has been 

 started. The offspring of the F4 generation have been tested by us 

 and permanent survival of mutually exchanged grafts was found 



* Institute "Rugjer Boskovic", by courtesy of Prof. N. Allegretti. 



