Drug-Induced Immunological Tolerance to Sheep Red Blood Cells in Mice: Effective Combination Therapy with Vincristine and Cyclophosphamide

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Abstract
Studies involving the combined use of cyclophosphamide (Cy) and vincristine (Vc) suggest a further step towards the induction of immunological unresponsiveness in mice sensitized with sheep red blood cells (SRBC). The usefulness of this combination has been confirmed by testing the effect of different timing and dosing schedules on the plaque-forming cell capacity as well as on the uptake of 14C-thymidine into spleen cell suspensions. A temporary but marked increase in DNA synthesis could be demonstrated in mice treated with a small dose of Vc 1 day after primary immunization with SRBC. Additional challenge with a single injection of 1 mg Cy per animal at this finite period of time resulted in complete immunotolerance, while a transient and partial immunosuppression occurred after treatment with either Vc or Cy alone. Two different patterns of tolerance could be defined: a short-term non-specific unresponsiveness lasting for about 2 weeks and an antigen-specific unresponsiveness lasting for about 6 weeks. The proposed explanation for this tolerance, induced by dose- and time-dependent administration of two cytostatic agents acting at various stages of the cell cycle might be a more intensive effect of Cy on immunocompetent cells growing (partially) synchronously after treatment with Vc.

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