Conversion of normal host splenocytes to suppressor cells by tumor-induced suppressor T-cell-derived factor(s): cyclophosphamide treatment reverses inhibitory activity.

Suppressor T (Ts) cells (or their factors) that arise in BALB/c mice as a consequence of fibrosarcoma cell growth can be adoptively transferred and can recruit new regulatory cells in vitro. In vivo temporal studies indicated that Ts cells significantly inhibited blastogenesis in normal host splenocytes as early as 4 h after adoptive transfer and lasted as long as 5 days. Suppressor T-cell-derived factor(s) did not suppress until 24 h after in vivo administration, and effects were protracted beyond time periods observed with Ts cells. Supernatants containing suppressor factor(s) not only significantly inhibited normal host spleen cell proliferation but also induced and/or recruited cells to become suppressive. Cyclophosphamide treatment of tumor-bearing hosts restored their in vitro spleen cell blastogenic ability and abolished in vitro suppression by Ts cells or their factors. This was confirmed in vivo by passive transfer experiments. Macrophage removal seemed to augment cyclophosphamide's ability to eliminate suppression.