Tumor promoters in conjunction with calcium ionophores mimic antigenic stimulation by reactivation of alloantigen-primed murine T lymphocytes.

摘要: Antigen binding to its specific receptor on T cells initiates a series of intracellular events that result in cell differentiation, activation, and clonal expansion. However, the mechanism by which these antigen-occupied receptors induce transmembrane signal transduction needs clarification. Because this appears involve an increase free Ca2+ concentration activation protein kinase C (PKC), we tested effect ionophores PKC activators alloantigen-specific primary mixed leukocyte culture cells. Both calcium ionophores, A23187 ionomycin, conjunction with 12-O-tetradecanoylphorbol 13-acetate (TPA) mimicked antigen or interleukin 2 (IL 2) inducing strong proliferative cytotoxic responses. In addition, ionophore TPA induced IL expression secretion. The capacity other phorbol esters non-phorbol ester tumor promoter (teleocidin) replace induction correlated their ability bind activate PKC. synergistic was blocked either chelator (EGTA) cAMP, is thought inhibit phosphatidylinositol metabolism. To determine whether activity mediated direct (Tc) secondary secretion activated helper (Th) cells, isolated populations cloned, Th Tc agents proliferation production but not Activation clones alone, resulted activity, could be anti-IL antibodies. results thus demonstrate increased can bypass provided antigen-receptor interaction does substitute for activating cytotoxicity