Glycodelin A triggers mitochondrial stress and apoptosis in T cells by a mechanism distinct and independent of TCR signaling

SundarRaj, Swathi and Mukhopadhyay, Debaditya and Karande, Anjali A (2008) Glycodelin A triggers mitochondrial stress and apoptosis in T cells by a mechanism distinct and independent of TCR signaling. In: Molecular Immunology, 45 (8). 2391 -2400.

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Abstract

Glycodelin A is one of the progesterone inducible endometrial factors that protect the fetal semiallograft from maternal immune rejection. Our previous studies demonstrate that glycodelin A induces apoptosis in activated T lymphocytes. Here, we report that glycodelin A initiates the intrinsic apoptotic program in T cells. Glycodelin A treatment triggers a stress response leading to mitochondrial membrane permeabilization and activation of initiator caspase 9. The kinetics of mitochondrial depolarization precede onset ofDNAfragmentation in both Jurkat cells and peripheral blood T cells treated with glycodelin A. Overexpression of the antiapoptotic protein Bcl-2 is sufficient to protect from glycodelin A-induced cell death. It has been reported earlier that glycodelin A desensitizes T cell receptor (TCR) signaling, probably by its association with the tyrosine phosphatase CD45. Here, we provide evidence that the apoptogenic activity of glycodelin A is not a consequence of this phenomenon. Glycodelin A-induced apoptosis does not depend on components of the TCR signal cascade, including CD45. We observe that glycodelin A is inhibitory to T cells even upon phorbol ester and ionophore stimulation which bypasses the TCR-proximal signaling events, and that glycodelin A treatment does not interfere with T cell activation as evidenced from induction of the activation marker CD69. Thus, glycodelin A initiates mitochondrial stress-mediated apoptosis in T cells by a pathway that is distinct and independent from the TCR signaling pathway.

Item Type:	Journal Article
Publication:	Molecular Immunology
Publisher:	Elsevier Ltd.
Additional Information:	Copyright of this article belongs to Elsevier Ltd.
Keywords:	Glycodelin;GdA;Placental protein 14 (PP14);Lipocalin;Fetal tolerance
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	14 May 2008
Last Modified:	19 Sep 2010 04:44
URI:	http://eprints.iisc.ac.in/id/eprint/13982

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