Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes

Soni, Chetna and Karande, Anjali A (2012) Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes. In: Human Reproduction, 27 (4). pp. 1005-1015.

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Abstract

The progesterone-regulated glycoprotein glycodelin-A (GdA), secreted by the decidualized endometrium at high concentrations in primates, inhibits the maternal immune response against fetal antigens and thereby contributes to the tolerance of the semi-allogenic fetus during a normal pregnancy. Our earlier studies demonstrated the ability of GdA to induce an intrinsic apoptotic cascade in CD4 T-lymphocytes and suppress the cytolytic effector function of CD8 T-lymphocytes. In this report, we investigated further into the mechanism of action of GdA controlling perforin and granzyme B expression in CD8 T-lymphocytes and the mechanism of action of GdA leading to lymphocyte death. Flow cytometry analysis was performed to check for the surface expression of interleukin-2 receptor (IL-2R) and intracellular eomesodermin (Eomes) in activated T-lymphocytes, whereas quantitative RTPCR analysis was used to find out their mRNA profile upon GdA treatment. Western analysis was carried out to confirm the protein level of Bax and Bcl-2. GdA reduces the surface expression of the high-affinity IL-2R complex by down-regulating the synthesis of IL-2R (CD25). This disturbs the optimal IL-2 signalling and decreases the Eomes expression, which along with IL-2 directly regulates perforin and granzymes expression. Consequently, the CD8 T-lymphocytes undergo growth arrest and are unable to mature into competent cytotoxic T-lymphocytes. In the CD4 T-lymphocytes, growth factor IL-2 deprivation leads to proliferation inhibition, decreased Bcl-2/enhanced Bax expression, culminating in mitochondrial stress and cell death. GdA spurs cell cycle arrest, loss of effector functions and apoptosis in different T-cell subsets by making T-lymphocytes unable to respond to IL-2.

Item Type:	Journal Article
Publication:	Human Reproduction
Publisher:	Oxford University Press
Additional Information:	Copyright of this article belongs to Oxford University Press.
Keywords:	glycodelin-A;CD25;eomesodermin;Bcl-2;Bax
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	01 May 2012 10:47
Last Modified:	03 May 2012 12:15
URI:	http://eprints.iisc.ac.in/id/eprint/44341

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