Suppression of Natural Cytotoxicity by Spleen Cells of Hydrocortisone-Treated Mice

Abstract The administration of hydrocortisone acetate (Hc) to (C57BL/6 × C3H)F1 or BALB/c mice by two daily i.p. injections (2.5 or 3.75 mg each) caused a substantial but transient reduction of splenic natural killer (NK) cell activity against YAC-1 lymphoma targets. This effect was not dependent on the thymus, since splenic NK activity declined in congenitally athymic BALB/c.nu/nu mice. The cytotoxic activity lowered in vivo by Hc could be partially restored in vitro simply by removing a subpopulation of cells adherent to, or phagocytic for, carbonyl particles. Thus, NK cells were reversibly suppressed in the spleens of Hc-treated mice. Despite removal of suppressor cells by carbonyl iron, filtration of splenocytes through Sephadex G-10 columns was ineffective. Moreover, the plastic-adherent, phagocyte-rich subpopulation of splenocytes was not enriched with suppressors. NK cells from untreated mice were suppressed in vitro by irradiated (2000 rads of γ-rays) and nonirradiated splenocytes of Hc-treated donors, and by cell-free superatants in which such cells were incubated. It thus appears that Hc activated presuppressor spleen cells to become suppressors within 48 hr. The paradox of suppressor cell removal by carbonyl iron but not by other adherence techniques does not allow characterization of such cells as to macrophage or lymphoid (pre-T or non-T) origin.