Thymic inhibition of myelopoietic proliferation

Homeostasis may be viewed as the dynamic balance reached between cellular production and loss. The effectors of proliferation are thought to be tissue-specific humoral substances. Inhibitory substances appear to negate the proliferate effects of activator substances. We report here that conditioned medium from cultures of murine "nonlymphoid" adherent thymus cells in a source of a potent myelopoietic inhibitor substance(s). Examination of the inhibitor(s) in the soft-agar clonogenic assay show it to abrogate both the 10-day granulocyte-macrophage colony-forming cell (GM-CFC) and the 25-day monocyte-macrophage colony-forming cell (M-CFC). The inhibition is most significant when the thymus-conditioned medium (TCM) is present upon culture initiation. TCM added at a time after soft-agar initiation (day 6) also results in significant clonogenic inhibition. We have characterized the inhibitor as potent on the basis that volume ratios of inhibitor to L-cell colony-stimulating factor (CSF) as low as 1 part to 40 parts will give near total inhibition of both GM-CFC and M-CFC clonogenic growth. The inhibitor is dialyzable, has a molecular weight of less than 1000, is not significantly cytotoxic, and its effects are reversible with washing.