Novel T cell function and specificity at the human maternal-fetal interface

Powell, Richard Morgan (2018). Novel T cell function and specificity at the human maternal-fetal interface. University of Birmingham. Ph.D.

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Abstract

The mechanisms by which immune tolerance is maintained during human pregnancy are unclear but include a range of modifications to the local and systemic maternal immune system. There is considerable T cell infiltration of the maternal decidua during pregnancy, however, the functional properties of this T cell response remains poorly defined.
We investigated the specificity and regulation of CD4+ and CDS+ T cells in human third trimester decidua and show that the ratio of highly differentiated effector to naive CD4+ and CDS+ T cells is increased markedly in comparison to peripheral blood. Decidual T cells were also found to display a unique functional profile with simultaneous production of interferon-y (IFN -y) and interleukin 4 (IL-4 ). Decidual T cells proliferated in response to fetal tissue, a function that was regulated by T regulatory cells, and HY -specific T cells with high levels ofProgrammed Death Protein 1 (PD-1) were detectable in the decidua of women with male pregnancies. Transcriptional analysis of CD4+ and CDS+ decidual T cells revealed a unique gene profile characterized by elevated expression of proteins associated with the response to interferon signaling. These data have considerable importance for the investigation of fetal-specific alloreactive immune responses within disorders of pregnancy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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