In the presence of 100 µg/ml of carrageenans (CAR), B6D2F1 responder spleen cells failed to generate anti-parent or anti-allogeneic cytotoxic T lymphocytes in vitro, but instead generated suppressor cells. Cultured CAR-treated cells added to mixtures of B6D2F1 anti-B6 or B6D2F1 anti-C3H cytotoxic effectors (induced in vitro) and the appropriate 51Cr-labeled lymphoma targets reduced or abolished cytolysis (measured as 51Cr release) depending on the ratio of suppressor to effector cells. Cultured spleen cells not exposed to CAR failed to inhibit both types of cytotoxicity.
Presuppressor cells were associated with a splenic subpopulation independent of the thymus (i.e., present in spleens of athymic nude mice), were moderately adherent to Sephadex G-10 columns, but were not phagocytic or “sticky” to carbonyl iron particles. Activation of such cells by CAR was not prevented by in vitro exposure to 2000 rads of γ-rays before culture, nor facilitated by antigenic stimulation. The matured suppressor cells remained radioresistant and became strongly adherent to Sephadex G-10. The suppressors lacked surface Thy-1 alloantigen detectable by antibody and rabbit complement. Suppressor cell activity was not restricted by the immunologic specificity and major histocompatibility type of effectors.
It would thus appear that CAR induced the transition from the presuppressor to the suppressor state of a macrophage-like splenic subpopulation via maturation, differentiation, or cell injury. Cells of this type, capable of inhibiting the effector arm of cell-mediated responses, may well contribute to the regulation of natural and induced cytotoxic cell interactions.
This work was supported by National Institutes of Health Research Grants AM-13969 and CA-12844, and by Contract N01-CM-53766 from the Division of Cancer Treatment, National Cancer Institute.