Inhibition of in vitro lymphocyte blastogenesis by inhibitor produced by cultured human lymphoblasts

Normal human lymphoblastoid cell lines, growing in continuous suspension culture, produce inhibitors of in vitro lymphocyte blastogenesis. The inhibitor reduces human lymphocyte blastogenic responses to phytohaemagglutinin, streptolysin O and the mixed lymphocyte culture 90-99%, is non cytotoxic and can inhibit both newly initiated and on going responses. The inhibitor is heat stable at 80°C but labile at 100°C, non dialysable and degraded by pronase but not DNase or RNase. It is species, and tissue specific and does not inhibit the proliferation of mouse lymphocytes, human melanoma cells or human bone marrow in vitro colony forming cells. Inhibitor was produced only under very specific conditions of crowding. Thus, maximal inhibitor production occurred at 5 x 10⁶ lymphocytes per cm² culture surface area while only 0-5% of the maximal amount was produced at 10⁶ or 5 x 10⁷ lymphoblasts per cm². This data is relevant to the nature of feedback control of immunological reactions and may guide the development of new classes of immunosuppressants.