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The splenic suppressor cell. I. Activity of thymus-dependent adherent cells: changes with age and stress.

The present study confirms and extends the finding that DA rat spleen cells include a subpopulation of adherent cells which act at high doses of phytohemagglutinin (PHA) or concanavalin H (ConA) to suppress DNA synthesis by other cells. Suppressor activity is lacking in spleens of doubly thymus-deprived rats. Mitomycin C treatment does not reduce the suppressor activity of normal whole spleen. It is inferred that the suppressor cell is a T lymphocyte or depends for its action on the presence of T lymphocytes and that its action does not require cell proliferation. DNA synthesis is much more affected by suppression at high mitogen levels than RNA or protein synthesis. A parallel is drawn between the separate regulation of DNA synthesis and other macromolecular synthesis in lymphocytes and so-called “pleiotypic” effects in other types of cells. Spleen cells of young rats give a relatively low response ( 3 H-thymidine uptake) to optimal or supraoptimal doses of PHA, which is markedly increased by removal of adherent cells on glass wool and is not affected by addition of purified macrophages. In contrast spleen cells of older animals give a high response, which falls when adherent cells are removed but is restored to the original level by addition of macrophages. It is concluded that older animals9 spleens differ from those of younger rats by a variable loss of suppressor cells and an increasing macrophage dependence of PHA-responsive cells. The former may account for the reported increase in autoantibody formation with age. Reactivity of cells of a given age was not affected by culturing them in young or old rat serum pools, respectively. Stress or injection of hydrocortisone acetate result in loss of suppressor cell adhesiveness to glass wool and increased macrophage dependence of PHA-responsive cells at 5 days. At 2 to 3 weeks there is a return to normal levels of adhesiveness and macrophage dependence, accompanied by a marked increase of suppressor activity. The 5-day changes are thought to reflect direct effects of steroid on the properties of T lymphocyte membranes, and the later changes altered levels of thymus hormone or possibly a surge of “post-thymic cells” into the peripheral lymphoid organs.