Reversal by citrovorum factor of methotrexate-induced suppression of cell-mediated and humoral immune response in mouse model systems.

C3H/HeHa mice were immunized (day 0) with 5 X 10(8) sheep red blood cells (SRBC) or 3 X 10(7) EL-4 lymphoma cells (i.p.), and C57B1/6J mice were immunized (day 0) with 3 X 10(7) P815 mastocytoma cells (i.p.). Methotrexate (MTX, 100 mg/kg) was given i.p. on day +2, with or without citrovorum factor (CF) at equimolar dose. In the absence of CF in C57B1/6J mice, the complement-independent cellular cytotoxicity (CICC) response did not recover in 18 days from MTX suppression to levels seen in immunized controls, while in C3H mice, with EL-4 as antigen, the response equalled that of controls by day 18 and was similar to or greater than that of controls through day 28; in both cases the serum antibody response returned to control levels by day 20. In both mouse strains, CF produced immediate recovery of the responses measured. In contrast, with SRBC as antigen, while the MTX suppression of complement-dependent cellular cytotoxicity (CDCC) in the absence of CF recovered by day 7, the CICC response recovered much more slowly. CF administration produced a rapid (day 4) return of CDCC activity to control levels, but only a partial restoration of CICC activity by day 6. In conclusion, the kinetics of recovery of the CICC and CDCC responses and of CF rescue of MTX-induced immunosuppression were dependent on mouse strain and on immunogens used, as well as on the type of response measured. Thus, selectivity of MTX action is indicated.