Bone marrow transplantation in the busulfan-treated rat. II. Effect of cyclophosphamide and antithymic serum on the presensitized state.

Abstract

The purpose of the present study was to develop a model in the busulfan (BU)-treated aplastic rat for investigating sensitization to donor marrow in various donor and recipient combinations differing in their degree of histocompatibility. In addition, cyclophosphamide (CY) and rabbit antirat thymocyte serum (RARTS) were studied as potential agents for reversing the presensitized state. Marrow transplantation was studied in the following donor-host combinations: ACI-Lewis (Ag-B-histoincompatible), F344-Lewis (Ag-B-histocompatible), and F344-LBNF1 ("very histocompatible"). The administration of 10(7) donor-type spleen cells i.v. 9 days before marrow infusion sensitized (prevented marrow takes) in all three systems. BN cells were able to sensitize Lewis recipients to F344 marrow because of minor antigens shared by the BN and F344 rat strains. RARTS given as six consecutive daily doses (1.5 ml each) beginning 1 day after immunization and ending 1 day before marrow grafting failed to abolish the presensitized states in all three systems studied. A single dose of CY (150 mg/kg), given alone or combined with RARTS, was able to reverse the measurable effects of presensitization in the histocompatible and "very histocompatible" situations, but was without effect on the histoincompatible system. The present studies were performed in a limited number of rat strain combinations, and the general and specific effects of CY on presensitization to minor histocompatibility antigens in other situations such as outbred mammalian systems remain to be determined.