Further studies on the induction of tolerance of skin homografts in rats

With the BN → Lewis rat strain combination it has been shown that the median survival time of skin homografts on three‐day‐old hosts (10.0 ± 0.5 days) does not differ significantly from that of similar grafts on adult animals. This rapid attainment of immunologic maturity has provided the basis for a sensitive test for the induction of tolerance of skin homografts. The putative tolerance‐conferring stimulus is injected intravenously at birth and the hosts are challenged with donor strain skin three days later. With this system it has been found that whereas an inoculum of 100,000 bone marrow cells elicited weak sensitization, as evidenced by a significant curtailment of graft survival, increasing the dosage to one million or more cells induced tolerance, as shown by prolongation of graft survival. The proportion of hosts displaying tolerance and its degree, increased with the cell dosage. When test‐grafting with skin was delayed until the hosts were 50–60 days old, the minimal number of cells required to confer tolerance was seven million. With the present assay it has been shown that the tolerance induced by low dosage cellular inocula wanes fairly rapidly, though the presence of a skin homograft from the third day onwards may prolong its duration. A previous finding that, with the present strain combination, bone marrow cells are significantly superior to either spleen or lymph node cells in conferring tolerance of skin homografts has been confirmed. It has been shown that adult thymocytes are only capable of inducing feeble degrees of tolerance over a wide dosage range (5 ‐ 50 × 10 6 ) and that thymocytes from infant donors are ineffective. Viable suspensions of epidermal cells and x‐irradiated or frozen‐thawed suspensions of bone marrow cells failed to confer tolerance, though it was induced fitfully by means of a microsomal lipoprotein extract of BN lymphoid tissue. Finally, it was shown that the survival of BN test grafts on three‐day‐old Lewis hosts was significantly prolonged if they were born of Lewis mothers specifically presensitized against BN antigens. This constitutes evidence of a passive transfer of the isoantibodies responsible for the phenomenon of immunological enhancement.