CD4+ T cells engrafted with a recombinant immunoreceptor efficiently lyse target cells in a MHC antigen- and Fas-independent fashion.
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.
Hombach
A
A
Clinic of Internal Medicine, Laboratory of Tumor Genetics, University of Köln, Josef-Stelzmann-Strasse 9, D-50932 Köln, Germany.
Heuser
C
C
Marquardt
T
T
Wieczarkowiecz
A
A
Groneck
V
V
Pohl
C
C
Abken
H
H
D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D006680:HLA Antigens / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D019169:Jurkat Cells; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D002272:Carcinoembryonic Antigen; D006680:HLA Antigens; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D019014:fas Receptor; D054353:Perforin