Pál Végh

Studies on the mechanism of transplantation tolerance: I. Do suppressor cells play a role in the induction and maintenance of neonatal transplantation tolerance?☆

Abstract Neonatal transplantation tolerance was induced in CBA ( H-2 k ) mice to A ( H-2 a ) mice by injection of (CBA × A)F 1 spleen cells. Animals carrying an A-skin test allograft for more than 4 months without any visible sign of rejection were considered to be permanently tolerant. Permanently tolerant CBA mice were given normal syngeneic spleen cells to abrogate the state of tolerance. Abrogation of tolerance was greatly facilitated by antithymocyte serum (ATS) treatment of tolerant mice prior to the normal syngeneic cell transfer. Survival of A allografts on normal, adult, ATS-treated CBA mice was significantly prolonged (and in many cases “adult” tolerance was achieved) by transfer of spleen cells of syngeneic mice made permanently tolerant at neonatal age. The possible role of the F 1 -cell “contamination” in the tolerance-inducing effect of the transferred “tolerant” spleen cells was excluded. The results indicate that ATS-sensitive suppressor cells play a definite role in the induction, maintenance, and transfer of neonatally induced transplantation tolerance.

Correlation of the in vivo and in vitro activities of antithymocyte sera (ATS) with the immunizing antigen dose.

SUMMARY Rabbits were immunized with 1, 3, 10, 30, 100, 300, or 1,000 × 106 murine thymocytes per kg according to the method of Levey and Medawar. Thus, 33 individual and 6 pooled anti-mouse antithymocyte serum (ATS) preparations were obtained and tested for in vivo immunosuppressive (graft-protective) as well as for in vitro thymocytotoxic activity. It was found that: (1) at least 3 × 106 thymocytes/kg were necessary for inducing ATS of appreciable immunosuppressive activity; (2) rabbits immunized with 30 × 106 thymocytes/kg supplied sera of the most potent immunosuppressive activity; (3) the increase of the immunizing antigen dose over 30 × 106 thymocytes/kg resulted in ATS preparations of decreased immunosuppressive activity; (4) the graft-protective activity of an ATS pool corresponded to the average of the activities of the individual ATS preparations from which the pool had been mixed, i.e., the process of pooling itself did not modify the immunosuppressive activity; and (5) there was a good correlation (r = 0.72, P < 0.001) between the in vivo immunosuppressive (graft-protective) activity and the in vitro thymocytotoxic titre of ATS preparations. The theoretical and practical significance of these results is discussed.