Abstract
The effect of syngeneic, allogeneic, and parental marrow infusions on busulfan (BU)-induced lethality in inbred and hybrid rats was investigated. BU had profound depressive effects on erythromyelopoietic tissues but modest effects on lymphatic tissues. Lewis (LEW) inbred rats given supra lethal doses of BU were protected from death by syngeneic but not by allogeneic Ag-B-compatible or-incompatible marrow from other inbred rat strains. The optimal time of marrow administration was 24 hours after BU injection, and the optimal amount of syngeneic marrow was between 16×106 and 32×106 nucleated marrow cells. LEWBNF1 [(LEW × BN)F1 rats were protected from supralethal doses of BU by syngeneic, parental (LEW and BN), F344 marrow (Ag-B compatible with LEW), but not by Ag-B-incompatible marrow. Chimerism for F344 cells was indicated in the LEWBNF1 rat by the demonstration of persistent levels of an F344-specific immunoglobulin allotype in the sera of such animals and by the specific tolerance to F344 skin allografts. Marrow from LEWBNF1 rats putatively chimeric for parental cells protected the appropriate (LEW or BN) rat from supralethal doses of BU, whereas marrow from normal LEWBNF1 rats did not. These observations indicated that LEWBNF1 rats given parental cells after BU injection were chimeric. Marrow transplantation in clinical aplastic anemia requires an immunosuppressive preparation. The BU-treated rat was only weakly immunosuppressed, and it may provide a useful model for the investigation of preparative immunosuppressive regimens in the aplastic host.
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