Activation of suppressor cells by low molecular weight factors secreted by spleen cells of tumor-bearing mice: modulatory role of prostaglandins.

We have shown previously that the spleens of mice bearing large M-1 fibrosarcomas contain inducer cells which secrete dialysable factors which activate suppressor T cells from unprimed, normal precursor spleen cells. Once activated, the suppressor cells inhibit the in vitro antibody synthesis of cocultured syngeneic splenocytes stimulated by T cell dependent antigens. In this paper we have examined the possibility that prostaglandins are involved in the activation process. Inducer and precursor cells were cultured in Marbrook vessels in chambers separated by dialysis membranes. Using this procedure, suppressor cells were activated following 12 h of culture but were not detectable after 6 h. The cyclooxygenase inhibitors, indomethacin, acetyl salicylic acid (ASA), and ibuprofen all prevented the activation of suppressor cells in a dose dependent manner. Prostaglandin (PG) E1, but not PGF2a or PGD2, restored the activation of suppressor cells in cultures containing the cyclooxygenase inhibitors. Restoration of suppressor cell activation was seen with 1 X 10(-7) M PGE1 but no activation of suppressor cells was seen in control cultures containing up to 1 X 10(-5) M PGE1. In addition, cultured spleen cells from tumor-bearing mice did not secrete higher quantities of PGE than did cells from age and sex matched normal mice. These data suggest that PGE has a modulatory rather than a direct role in the activation of suppressor cells by inducer factors from tumor-activated inducer cells.