Human lymphoblastoid cell lines, cultured under conditions of crowding, produce an inhibitor of in vitro lymphocyte blastogenic responses to phytohemagglutinin, streptolysin O, and the mixed lymphocyte reaction. On a per cell basis, maximum inhibitor is produced by 5 X 108 lymphoblasts/cm2 of culture surface area. None is produced by 1 X 106 cells/cm2 and little is produced per cell by concentrations of 5 X 107 or above. Inhibitor is produced maximally from 24 or 48 to 72 hr after the cells are placed under conditions of crowding. Inhibitor is produced when the cells have between 10 and 15% of their maximal proliferative thrust and ceases when proliferation stops. Inhibitor production is blocked by puromycin, cycloheximide, actinomycin D, arabinosylcytosine, and arabinosyl-6-mercaptopurine, indicating that both proliferation and protein synthesis are required. Little inhibitor is produced by either unstimulated or mitogen-stimulated, freshly collected human peripheral blood lymphocytes even when cultured under similar conditions of crowding. These observations are relevant to an understanding of feedback control in proliferating lymphoid tissues.
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