Evidences are accumulating that CD4
+ T cells can physiologically mediate antigen specific target cell lysis. By circumventing major histocompatibility complex (MHC)-restrictions through an engineered chimeric antigen receptor (CAR), CD4
+ T cells lyse defined target cells as efficiently as do CD8
+
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Evidences are accumulating that CD4
+ T cells can physiologically mediate antigen specific target cell lysis. By circumventing major histocompatibility complex (MHC)-restrictions through an engineered chimeric antigen receptor (CAR), CD4
+ T cells lyse defined target cells as efficiently as do CD8
+ T cells. However, the cytolytic capacity of redirected CD4
+CD25
− T cells, in comparison with CD4
+CD25
+ regulatory T (Treg) cells was so far not thoroughly defined. Treg cells require a strong CD28 signal together with CD3ζ for activation. We consequently used a CAR with combined CD28CD3ζ signalling for redirecting CD4
+CD25
− T cells and CD4
+CD25
+ Treg cells from the same donor. CAR redirected activation of these T cell subsets and induced a distinct cytokine pattern with high IL-10 and a lack of IL-2 release by Treg cells. Despite strong antigen-specific activation, CAR Treg cells produced only weak target cell lysis, whereas CD4
+CD25
− CAR T cells were potent killers. Cytolysis did not correlate with the target cell sensitivity to Fas/FasL mediated killing; CD4
+CD25
− T cells upregulated perforin and granzyme B upon CAR activation, whereas Treg cells did less. The different cytolytic capacities of CAR redirected conventional CD4
+ cells and Treg cells imply their use for different purposes in cell therapy.
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