Most Do, but Some Do Not: CD4+CD25− T Cells, but Not CD4+CD25+ Treg Cells, Are Cytolytic When Redirected by a Chimeric Antigen Receptor (CAR)
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Department I Internal Medicine, University Hospital Cologne, Cologne D-50931, Germany
2
Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, Cologne D-50931, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Vita Golubovskaya
Cancers 2017, 9(9), 112; https://doi.org/10.3390/cancers9090112
Received: 30 June 2017
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Revised: 20 August 2017
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Accepted: 22 August 2017
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Published: 29 August 2017
(This article belongs to the Special Issue CAR-T Cell Therapy against Different Types of Cancer)
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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Keywords:
CAR; chimeric antigen receptor; T cell; CD4; Treg cell
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MDPI and ACS Style
Hombach, A.A.; Abken, H. Most Do, but Some Do Not: CD4+CD25− T Cells, but Not CD4+CD25+ Treg Cells, Are Cytolytic When Redirected by a Chimeric Antigen Receptor (CAR). Cancers 2017, 9, 112. https://doi.org/10.3390/cancers9090112
AMA Style
Hombach AA, Abken H. Most Do, but Some Do Not: CD4+CD25− T Cells, but Not CD4+CD25+ Treg Cells, Are Cytolytic When Redirected by a Chimeric Antigen Receptor (CAR). Cancers. 2017; 9(9):112. https://doi.org/10.3390/cancers9090112
Chicago/Turabian StyleHombach, Andreas A., and Hinrich Abken. 2017. "Most Do, but Some Do Not: CD4+CD25− T Cells, but Not CD4+CD25+ Treg Cells, Are Cytolytic When Redirected by a Chimeric Antigen Receptor (CAR)" Cancers 9, no. 9: 112. https://doi.org/10.3390/cancers9090112
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