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Cancers 2017, 9(9), 112; https://doi.org/10.3390/cancers9090112

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)

1
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
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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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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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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