Universität zu Köln

Franklin, Cindy, Bruderek, Kirsten, Schilling, Bastian and Brandau, Sven (2019). Chemoirradiated neutrophils and T cells differentially affect immune functions of APCs. J. Leukoc. Biol., 106 (2). S. 481 - 494. HOBOKEN: WILEY. ISSN 1938-3673

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Abstract

Extracorporeal photopheresis (ECP) is known as an immunomodulatory therapy with few side effects, which is mainly used in the treatment of cutaneous T cell lymphoma, graft-versus-host disease, and allograft rejection. During ECP, leukocytes are separated from whole blood by leukapheresis, subsequently chemoirradiated with 8-methoxypsoralen and UVA light, and re-infused into the patient. Although clinically effective, its mode of action has not been fully elucidated. In the present study, we analyzed the interaction of chemoirradiated neutrophils and CD3+ lymphocytes with APC in an in vitro model. We report that chemoirradiated CD3+ T cells induced increased expression of activation markers on dendritic cells (DC), macrophages, and monocytes. Coculture of chemoirradiated CD3+ T cells with these APC also led to significantly increased secretion of TNF-alpha. Although less pronounced, additional activation of APC took place when APC were stimulated with LPS or IFN-gamma. In contrast, chemoirradiated neutrophils did not show activating effects on APC. The presence of chemoirradiated neutrophils during LPS and IFN-gamma stimulation of DC rather diminished DC and macrophage activation. In line with these findings DC cocultured with chemoirradiated CD3+ T cells, but not neutrophils, showed significantly increased activation of CD3+ responder lymphocytes in a mixed lymphocyte reaction. With this study, we demonstrate that chemoirradiated leukocytes have differential indirect immunomodulatory effects. Whereas chemoirradiated CD3+ T cells activate APC, chemoirradiated neutrophils suppress activation of APC in the presence of other activating factors, suggesting that the composition of the ECP-treated buffy coat might be of importance for its immunomodulatory effects.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Franklin, Cindy UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruderek, Kirsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Schilling, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandau, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133878
DOI:	10.1002/JLB.5A0618-242R
Journal or Publication Title:	J. Leukoc. Biol.
Volume:	106
Number:	2
Page Range:	S. 481 - 494
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1938-3673
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VERSUS-HOST-DISEASE; APOPTOTIC CELLS; EXTRACORPOREAL PHOTOPHERESIS; DENDRITIC CELLS; CYTOKINE PRODUCTION; PHOTOCHEMOTHERAPY; MATURATION; 8-METHOXYPSORALEN; ULTRAVIOLET; MECHANISMS Multiple languages Cell Biology; Hematology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13387