Calcium and inositolphosphates in the activation of T cell-mediated cytotoxicity.
Reports from a number of laboratories have shown that mAbs against the T3-Ti receptor complex cause an increase in cytosolic-free Ca2+ [( Ca2+]i) and the hydrolysis of phosphatidylinositolbisphosphate (PIP2) in CTLs. In the present report we show that activation of CTLs by their specific targets causes: (a) release of Ca2+ from intracellular stores; (b) transient formation of inositol trisphosphate (InsP3); and (c) an increased permeability to Ca2+ of CTL plasma membrane. Killing of unrelated targets could be induced by cocentrifugation of the unrelated targets with CTLs in the presence of A23187 or PMA. We conclude that: (a) activation of CTLs by specific antigens triggers the generation of the same intracellular mediators generated by stimulation of lymphocytes with anti-T3-Ti receptor antibodies and/or with polyclonal mitogens; and (b) intracellular signals that mediate the delivery of the lethal hit by CTLs are indistinguishable from those that induce cell proliferation.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D004533:Egtazic Acid / Q000494:pharmacology; D005453:Fluorescence; D017988:Gammaretrovirus; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000209:etiology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008980:Moloney murine sarcoma virus / Q000276:immunology; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014412:Tumor Virus Infections
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D000001:Calcimycin; D004533:Egtazic Acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium