REGULATORY SUBSTANCES PRODUCED BY LYMPHOCYTES .5. PRODUCTION OF INHIBITOR OF DNA-SYNTHESIS (IDS) BY PROLIFERATING T LYMPHOCYTES

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 118  (4) , 1379-1384
Abstract
The conditions necessary for production of inhibitor of DNA synthesis (IDS) by rat lymphocytes were investigated. In concanavalin A (Con A)-stimulated lymph node cell (LNC) cultures, IDS production was not detected in the culture supernatant during the first 24 h, and it increased gradually after that to reach a maximum at 3-4 days. When the cells were pretreated with mitomycin C, IDS was not produced, suggesting that DNA synthesis of LNC or a LNC subpopulation is necessary for IDS production. Con A-stimulated spleen cells produced a high level of IDS within 24 h, and its production fell off sharply thereafter. Con A-stimulated rat thymocytes also produced IDS reaching a maximum at 2-3 days. Thymus cells from rats treated with hydrocortisone 48 h previously did not produce IDS. Cortisol-sensitive (cortical) thymocytes are probably capable of producing IDS and cortisol-resistant (medullary) thymocytes are not. IDS production by lymphoblasts was proportional to cell number, and production was unaffected by cell density (1 to 10 .times. 106/ml) or by the concomitant presence of normal cells from spleen, lymph node or thymus. Con A-stimulated cells, after becoming blasts, appear to produce IDS automatically without affecting or being affected by other cells. Spleen and thymus cells from rats injected with a large dose of antigen (ovalbumin, 100 mg, i.p.) 24 h in advance produced substantial amounts of IDS in culture within 24 h in the absence of mitogen or additional antigen; the cells from rats injected with an immunizing dose (1 mg) of the same antigen did not produce IDS. The cells producing IDS in the spleen were adherent to glass wool; those in the thymus were partially adherent. IDS production by antigen-stimulated spleen cells was abrogated by injecting rats with bromodeoxyuridine (BUdR) at 0 and 12 h after the ovalbumin. Apparently, a subpopulation of adherent spleen cells (possibly resembling cortical thymocytes), which begins to proliferate within a few hours after a large dose of systemic antigen, produces IDS. This may account for increased nonspecific suppressor activity observed at the same time.