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Updated: May 13, 2026

Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface
Published on: May 21, 2015
CD8+ effector T cells at the fetal-maternal interface, balancing fetal tolerance and antiviral immunity
Tamara Tilburgs1, Jack L Strominger
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. tilburgs@FAS.Harvard.edu
During pregnancy CD8+ effector T cells need optimal immune regulation to prevent a detrimental response to allogeneic fetal cells while providing immune protection to infections. A significant proportion of (prospective) mothers carry naïve or memory CD8+ T cells with a TCR that can directly bind to paternal MHC molecules. In addition, a high percentage of pregnant women develop specific T cell responses to fetal minor histocompatibility antigens (mHags). Under normal conditions, fetal-maternal MHC and mHag mismatches lead to elevated lymphocyte activation but do not induce pregnancy failure. Furthermore, viral infections alter the maternal CD8+ T cell response by changing the CD8+ T cell repertoire and increasing the influx of CD8+ T cells to decidual tissue. The normally high T cell activation threshold at the fetal-maternal interface may prevent efficient clearance of viral infections. Conversely, the increased inflammatory response due to viral infections may break fetal-maternal tolerance and lead to pregnancy complications. The aim of this review is to discuss the recent studies of CD8+ T cells in pregnancy, identify potential mechanisms for antigen-specific immune recognition of fetal extravillous trophoblast (EVT) cells by CD8+ T cells, and discuss the impact of viral infections and virus-specific CD8+ T cells during pregnancy.
During pregnancy CD8+ effector T cells need optimal immune regulation to prevent a detrimental response to allogeneic fetal cells while providing immune protection to infections. A significant proportion of (prospective) mothers carry naïve or memory CD8+ T cells with a TCR that can directly bind to paternal MHC molecules. In addition, a high percentage of pregnant women develop specific T cell responses to fetal minor histocompatibility antigens (mHags). Under normal conditions, fetal-maternal MHC and mHag mismatches lead to elevated lymphocyte activation but do not induce pregnancy failure. Furthermore, viral infections alter the maternal CD8+ T cell response by changing the CD8+ T cell repertoire and increasing the influx of CD8+ T cells to decidual tissue. The normally high T cell activation threshold at the fetal-maternal interface may prevent efficient clearance of viral infections. Conversely, the increased inflammatory response due to viral infections may break fetal-maternal tolerance and lead to pregnancy complications. The aim of this review is to discuss the recent studies of CD8+ T cells in pregnancy, identify potential mechanisms for antigen-specific immune recognition of fetal extravillous trophoblast (EVT) cells by CD8+ T cells, and discuss the impact of viral infections and virus-specific CD8+ T cells during pregnancy.
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