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CD4⁺ T Cells Engrafted with a Recombinant Immunoreceptor Efficiently Lyse Target Cells in a MHC Antigen- and Fas-Independent Fashion¹

Andreas Hombach^*, Claudia Heuser^*, Thomas Marquardt^*, Anja Wieczarkowiecz^*, Volker Groneck^*, Christoph Pohl and Hinrich Abken^2,*

^* Klinik I für Innere Medizin, Labor Tumorgenetik, Universität zu Köln, Köln, Germany; and St. Elisabeth-Krankenhaus Köln-Hohenlind, Köln, Germany

T cells engrafted by a recombinant immunoreceptor with predefined Ag specificity can efficiently lyse Ag-positive target cells in a MHC Ag-independent manner. It is yet unresolved how receptor-grafted CD4⁺ T cells contribute to MHC Ag-independent target cell lysis. To address this issue, we grafted isolated CD8⁺ and CD4⁺ T cells from the peripheral blood with recombinant anti-carcinoembryonic Ag and anti-CD30 receptors, respectively. Cytotoxicity analyses revealed that grafted CD4⁺ T cells exert cytolysis of Ag-positive target cells with an efficiency similar to that of grafted CD8⁺ T cells. Lysis by receptor-grafted CD4⁺ T cells is Ag specific and is inhibited by blocking the target Ag or the Ag binding site of the recombinant receptor. Both Fas-sensitive and Fas-resistant target cells are lysed with equal efficiency, and lysis of Fas-sensitive target cells is not blocked by an anti-Fas ligand Ab, indicating that cytolysis by receptor-grafted CD4⁺ T cells is independent of the Fas pathway. We conclude that cytolysis by CD4⁺ T cells equipped with a recombinant immunoreceptor is MHC Ag and Fas independent and likely to be mediated by perforin present in receptor-grafted CD4⁺ T cells.

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