The effect of timing of skin grafts on subsequent survival in ALS-treated, marrow-infused mice.

It has previously been shown that the survival of C3H/He skin grafts can be prolonged on ALS-treated (C57 x A)F1 mice by the injection of C3H/He bone marrow cells 7 days after grafting. Experiments have now been done to study the influence of timing of the skin graft on its subsequent survival. Single grafts were placed either before or after marrow was given. Paired grafts on the same animal were also studied, one placed before and one after marrow was given. Grafts placed before marrow was given, whether single or paired, showed equal and significant prolongation while grafts placed after marrow was given showed only slight prolongation compared with ALS controls. Paired grafts showed distinctly different survival curves depending on their time of placement in relation to injection of marrow. The pattern of graft survival suggests that the graft prolongation achieved is attributable to a mechanism similar to enhancement. Experiments were also done to see whether a state of preexisting immunity to the skin graft donor induced by the injection of marrow could be manipulated to achieve prolonged graft survival. (C57 x A)F1 mice were treated with ALS, given injections of C3H/He marrow, and grafted 56 days later with C3H/He skin either with or without additional ALS at the time of grafting. If no ALS was given grafts were rejected in accelerated fashion, indicating that the previous injection of marrow had sensitized the recipient. With additional ALS, the prolongation of graft survival achieved far exceeded that seen using our standard protocol of skin grafting a week before marrow is given. This represents one of the first demonstrations of positive alteration of a preexisting state of immunity to achieve graft prolongation which exceeds that expected by giving ALS immunosuppression alone to a presensitized animal.