Universität zu Köln

Tischner, Denise, Theiss, Jennifer, Karabinskaya, Anna, van den Brandt, Jens, Reichardt, Sybille D., Karow, Ulrike, Herold, Marco J., Luehder, Fred, Utermoehlen, Olaf and Reichardt, Holger M. (2011). Acid Sphingomyelinase Is Required for Protection of Effector Memory T Cells against Glucocorticoid-Induced Cell Death. J. Immunol., 187 (9). S. 4509 - 4517. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

Full text not available from this repository.

Abstract

The activity of acid sphingomyelinase (aSMase) was previously reported to be involved in glucocorticoid-induced cell death (GICD) of T lymphocytes. This mechanism in turn is believed to contribute to the therapeutic efficacy of glucocorticoids (GCs) in the treatment of inflammatory diseases. In this study, we reassessed the role of aSMase in GICD by using aSMase knockout mice. The absence of aSMase largely abolished the partial protection that effector memory CD4(+) T cells in wild-type mice possess against GICD. Reduced IL-2 secretion by aSMase-deficient CD4(+) T cells suggested that a lack of this important survival factor might be the cause of these cells' enhanced susceptibility to GICD. Indeed, addition of IL-2 restored the protection against GICD, whereas neutralization of IL-2 abrogated the otherwise protective effect seen in wild-type effector memory CD4(+) T cells. The therapeutic implications of the altered sensitivity of aSMase-deficient T cells to GICD were assessed in models of inflammatory disorders; namely, experimental autoimmune encephalomyelitis and acute graft-versus-host disease. Surprisingly, GC treatment was equally efficient in both models in terms of ameliorating the diseases, regardless of the genotype of the T cells. Thus, our data reveal a hitherto unrecognized contribution of aSMase to the sensitivity of effector memory CD4(+) T cells to GICD and call into question the traditionally attributed importance of GICD of T cells to the treatment of inflammatory diseases by GCs. The Journal of Immunology, 2011, 187: 4509-4516.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tischner, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Theiss, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Karabinskaya, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Brandt, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Reichardt, Sybille D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Karow, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Herold, Marco J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Luehder, Fred UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Reichardt, Holger M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-486680
DOI:	10.4049/jimmunol.1100911
Journal or Publication Title:	J. Immunol.
Volume:	187
Number:	9
Page Range:	S. 4509 - 4517
Date:	2011
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	1550-6606
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VERSUS-HOST-DISEASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INDUCED APOPTOSIS; MULTIPLE-SCLEROSIS; RECEPTOR; THYMOCYTES; CD28; ACTIVATION; DEFICIENT; SURVIVAL Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48668