A. Hombach et al., CD4(+) T cells engrafted with a recombinant immunoreceptor efficiently lyse target cells in a MHC antigen- and Fas-independent fashion, J IMMUNOL, 167(2), 2001, pp. 1090-1096
T cells engrafted by a recombinant immunoreceptor with predefined Ag specif
icity can efficiently lyse Ag-positive target cells in a MHC Ag-independent
manner. It is yet unresolved how receptor-grafted CD4(+) T cells contribut
e to MHC Ag-independent target cell lysis. To address this issue, we grafte
d isolated CD8(+) and CD4(+) T cells from the peripheral blood with recombi
nant anti-carcinoembryonic Ag and anti-CD30 receptors, respectively. Cytoto
xicity 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 inh
ibited 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-graf
ted CD4(+) T cells.