Drug-induced immunological unresponsiveness: selective inhibition of T-cell 'helper function' by cyclophosphamide in mice pretreated with phytohaemagglutinin.

Studies involving the combined use of phytohaemagglutinin (PHA) and cyclophosphamide (CY) indicate that both agents can act together to produce immunological unresponsiveness: following injection of PHA into mice, splenic DNA synthetic responses [14C]thymidine incorporation) and haemolysin plaque formation against sheep red blood cells were determined in daily intervals. Both immunosuppression and DNA synthetic activity were maximally developed 5 days after treatment with PHA. Administration of CY at this time resulted in immunological unresponsiveness lasting for about 18 days. Antibody production could be completely restored with antigen-activated T cells (but not with B cells), thus indicating a selective inhibition of T-cell 'helper function' in mice treated with PHA and CY. This observation is consistent with the general assumption that cells involved in the response to PHA are predominantly T cells. Apparently, these cells are highly sensitive to an inactivation by CY after stimulation with PHA.