Inhibition of proliferation without affecting the generation of cytotoxicity in the human mixed lymphocyte reaction

摘要: Abstract Phosphoramide mustard (PM) is considered to be the major tumoricidal metabolite of cyclophosphamide in vivo . The effects this vitro on several immune functions human lymphocytes have been investigated. Very low concentrations (10 −7 10 M ) PM added lymphocyte cultures inhibited proliferation response mitogens and alloantigens. At these concentrations, inhibition appeared due a direct action proliferative cells. Thus, concanavalin A-stimulated still acquired IL-2 receptors (Tac antigen) normally presence −6 −9 ). Only exceedingly high −5 or greater) prevented acquisition Tac antigen. Similarly, was probably not related endogenous levels: addition exogenous PM-containing did result any restoration proliferation. Further evidence that directly affected cells T continuously growing IL-2. exposure time necessary for essentially identical those lymphoproliferative responses Paradoxically, however, generation cytotoxic mixed reactions (MLRs) tumor cell (MLTCs) very resistant PM. In parallel MLRs MLTCs were approximately 1000-fold more than responses. at inhibited. These data suggest clonal expansion their precursors by an absolute requirement cytolytic activity.