Universität zu Köln

Ansprenger, Christian ORCID: 0000-0001-8685-3415, Vogt, Valentin, Schick, Julia, Hirn-Lopez, Annika, Vokac, Yvonne, Harabacz, Ihor, Braeu, Marion, Kroell, Tanja, Karenberg, Axel, Kolb, Hans-Jochem and Schmetzer, Helga (2018). Paramunity-inducing Factors (PINDs) in dendritic cell (DC) cultures lead to impaired antileukemic functionality of DC-stimulated T-cells. Cell. Immunol., 328. S. 33 - 49. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2163

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Abstract

Introduction: Paramunity-inducing-Factors (PINDs) consist of attenuated/inactivated viruses of various poxvirus-genera, used in veterinary medicine as non-antigen-specific, non-immunising stimulators of the innate immune system against infectious and malignant diseases. Their danger-signaling-interactions were tested for their capacity to improve leukemic antigen-presentation on DC generated from AML-patients' blasts ('DCleu') and DC-stimulation/activation of antileukemic T-cells. Methods: We analyzed, whether the addition of PINDs during DC cultures (15 healthy, 22 leukemic donors) and mixed lymphocyte culture (MLC, n = 15) with autologous (n = 6), allogeneic (n = 2) or T-cells after stem cell transplantation (SCT; n = 7) would alter the quality and quantity of DC, the composition of T-cell-subsets, and/or their antileukemic functionality (AF) as studied by FACS and functional Fluorolysis-cytotoxicity-assays. Results: Effects on 1. DC-cultures: PINDs in DC-cultures lead to increased proportions of mature DC and DCleu but reduced proportions of viable and overall, as well as TLR4- and TLR9-expressing DC. 2. MLC: PINDs increased early (CD8+) T-cell activation (CD69+), but reduced proportions of effector-T-cells after MLC 3. AF: Presence of PINDs in DC- and MLC-cultures reduced T-cells' as well as innate cells' antileukemic functionality. 4. Cytokine-release profile: Supernatants from PIND-treated DC- and MLC-cultures resembled an inhibitory microenvironment, correlating with impaired blast lysis. Conclusions: Our data shows that addition of PINDs to DC-cultures and MLC result in a blast-protective-capacity leading to impaired AF, likely due to changes in the composition of T-/innate effector cells and the induction of an inhibitory microenvironment. PINDs might be promising in treating infectious diseases, but cannot be recommended for the treatment of AML-patients due to their inhibitory influence on antileukemic functionality.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ansprenger, Christian UNSPECIFIED orcid.org/0000-0001-8685-3415 UNSPECIFIED Vogt, Valentin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schick, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hirn-Lopez, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Vokac, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Harabacz, Ihor UNSPECIFIED UNSPECIFIED UNSPECIFIED Braeu, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroell, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Karenberg, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kolb, Hans-Jochem UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmetzer, Helga UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-185502
DOI:	10.1016/j.cellimm.2018.03.005
Journal or Publication Title:	Cell. Immunol.
Volume:	328
Page Range:	S. 33 - 49
Date:	2018
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2163
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE MYELOID-LEUKEMIA; ANTIGEN-PRESENTING CELLS; SMALLPOX VACCINATION; IMMUNE-RESPONSES; IMMUNOTHERAPY; CANCER; AML; BLASTS; TRANSPLANTATION; GENERATION Multiple languages Cell Biology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18550