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Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
Glycodelin A suppresses the cytolytic activity of CD8+ T lymphocytes
Chetna Soni1, Anjali A Karande
1Department of Biochemistry, Indian Institute of Science, Bangalore-560012, India.
Maternal tolerance to the semi-allogenic fetus is brought about by several mechanisms in humans. Glycodelin A (GdA), secreted by the uterine mucosa and decidua is induced to high levels by progesterone between 12 and 16 weeks of pregnancy. The glycoprotein, an immunomodulator has been shown to be inhibitory to the survival and functions of almost all the immune cells. CD8(+) T cells which predominate the T lymphocyte population in the decidua are relatively less studied. We attempted to find out the possible mechanism, if any, of regulation of the cytolytic function of CD8(+) T cells during pregnancy. Alloactivated CD8(+) T cells harbouring specific cytolytic activity against target cells exhibited compromised activity upon treatment with high concentrations of GdA. Interestingly, unlike the CD4(+) T cells, CD8(+) T cells were resistant to GdA-induced apoptosis. The inhibition of cytotoxic T lymphocyte activity was brought about by the downregulation of transcription of the cytolytic effector molecules, granzyme B and perforin and the degranulation of cytolytic vesicles. These results suggest a protective role played by GdA during pregnancy by regulating the cytolytic activity of CD8(+) T cells.
Maternal tolerance to the semi-allogenic fetus is brought about by several mechanisms in humans. Glycodelin A (GdA), secreted by the uterine mucosa and decidua is induced to high levels by progesterone between 12 and 16 weeks of pregnancy. The glycoprotein, an immunomodulator has been shown to be inhibitory to the survival and functions of almost all the immune cells. CD8(+) T cells which predominate the T lymphocyte population in the decidua are relatively less studied. We attempted to find out the possible mechanism, if any, of regulation of the cytolytic function of CD8(+) T cells during pregnancy. Alloactivated CD8(+) T cells harbouring specific cytolytic activity against target cells exhibited compromised activity upon treatment with high concentrations of GdA. Interestingly, unlike the CD4(+) T cells, CD8(+) T cells were resistant to GdA-induced apoptosis. The inhibition of cytotoxic T lymphocyte activity was brought about by the downregulation of transcription of the cytolytic effector molecules, granzyme B and perforin and the degranulation of cytolytic vesicles. These results suggest a protective role played by GdA during pregnancy by regulating the cytolytic activity of CD8(+) T cells.
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