Dr. S. Scherjon

Fetus specific T cell modulation during fertilization, implantation and pregnancy.

Workshop Leaders: Dr. S. Scherjon

Department: Department of Obstetrics, Leiden University Medical Center

One of the poorly understood enigma of human reproduction is the uncomplicated acceptance of the mother of her antigenetically strange (semi-allogeneic) fetus. The model of pregnancy and semi-allogeneic acceptance is an interesting model for transplantation biology. There is now recent experimental evidence -which supports epidemiological data- that already before implantation of pregnancy, fetus specific tolerance is induced for paternally derived antigens. The importance of T cells function, locally active in the the decidual lining of the human uterus, is only recently appreciated, also because of the possibility of immunological memory.

The expression of paternal antigens on invading fetal trophoblast and their interaction with both uterine NK cells and T cells, might be responsible for a non-specific and a specific suppression of the cytotoxic T cell respons. Also the possible role of immunomodulatory macrophages, being part of an immunological network in the uterus during human pregnancy, will be discussed in the line of tolerance induction.

Mouse models of recurrent spontaneous miscarriage have suggested an important role for regulatory T cells. In detail the model of activation in humans of these regulatory T cells (both CD4+ and CD8+ T regs) will be discussed and experimental evidence will be analyzed. Different techniques such as FACS analysis, immunohistochemistry and genetic polymorphisms will be discussed not only to demonstrate the presence of these cells but also their function.

This workshop will give tools for the understanding of specific tolerance induction and will shed light on new possible tolls also for the induction of these mechanism in the transplantation, hopefully leading to newer medication strategies precluding the use of pharmacological immuno-suppression.