Tolerance Induction and Sensitization by Preincubation of Bone Marrow With Allogeneic Erythrocytes

Summary

In vitro preincubation of donor bone marrow with allogeneic erythrocytes greatly influenced the success of bone marrow transplantation into lethally irradiated recipients. The effect was the abolition of the graft-versus-host reaction, diminution of the severity of the reacti on, or an increased reactivity, depending on the antigenic relationships among the marrow donors, the erythrocytes, and the various recipients. Unresponsiveness or tolerance resulted when the recipient was as immunogenic or less immunogenic than the erythrocytes used in the incubation as “priming” antigen for the bone marrow. However, when the recipient was more immunogenic than the erythrocyte donor strain, a graft-versus-host reaction of varying degrees of severity occurred. From these observations, the concept that antigenicity (or immunogenicity) can be ranked was developed. A direct relationship was established between tolerance and sensitization by demonstration of a graded responsiveness from the unresponsive state, through varying degrees of responsiveness, to an accelerated response (sensitization).