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Cancers 2017, 9(9), 112;

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)

Department I Internal Medicine, University Hospital Cologne, Cologne D-50931, Germany
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
Received: 30 June 2017 / Revised: 20 August 2017 / Accepted: 22 August 2017 / Published: 29 August 2017
(This article belongs to the Special Issue CAR-T Cell Therapy against Different Types of Cancer)
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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. View Full-Text
Keywords: CAR; chimeric antigen receptor; T cell; CD4; Treg cell CAR; chimeric antigen receptor; T cell; CD4; Treg cell

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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.

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