EFFECT OF CYCLOPHOSPHAMIDE AND METHYLPREDNISOLONE ON IN VITRO CELLULAR IMMUNE RESPONSE TO ALLOGENEIC TUMOR CELLS CORRELATION WITH IN VIVO REJECTION

Abstract

The immunosuppressive effects of methylprednisolone (MP, 5 mg/kg) and cyclophosphamide (CY, 180 and 48 mg/kg) on cellular immune responses to allogeneic tumor [mouse lymphoma MBL2] cells were evaluated using in vitro tests. The variations in the number of splenocytes and the in vivo response to the injection of allogeneic tumor cells (rejection or facilitation) were recorded. The drugs were administered [to mice] at different times in relation to immunization. Polyclonal stimulation essentially reflected T [thymus derived] cell recovery, whereas monoclonal stimulation was depressed when the drugs were administered at the time of immunization, suggesting a defect at the level of sensitization. MP had little effect on cytotoxicity but was associated with allograft facilitation. CY strongly inhibited the specific activity of cytotoxic lymphocytes when administered at the time of inoculation, but this was associated with normal graft rejection. Reduced numbers of T cells and increased cytotoxicity was recorded when both drugs were administered 2 days prior to immunization. Thus, this study showed that MP-induced facilitation does not correlate with the levels of in vitro cytotoxicity; demonstrated a dissociation of the effect of CY on in vitro cytotoxicity and the in vivo response when given at the time of immunization; and confirmed the hypothesis that CY enhances T cell responses when given 2 days before immunization, with similar observations being extended to MP treatment. The cytotoxicity observed at that time was probably responsible for graft rejection.