Universität zu Köln

Hombach, Andreas A. and Abken, Hinrich (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 (9). BASEL: MDPI. ISSN 2072-6694

Full text not available from this repository.

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 CD3 zeta for activation. We consequently used a CAR with combined CD28CD3 zeta 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-218408
DOI:	10.3390/cancers9090112
Journal or Publication Title:	Cancers
Volume:	9
Number:	9
Date:	2017
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GRANZYME-B; ESTABLISHED MELANOMA; ACTIVATION; INFECTION; PERFORIN; IL-2; LYMPHOCYTES; SUPPRESSION; EXPRESSION; FASL Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21840