Fetal–maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells

Tilburgs, Tamara; Scherjon, Sicco A.; van der Mast, Barbara J.; Haasnoot, Geert W.; Versteeg-v.d.Voort-Maarschalk, Minke; Roelen, Dave L.; van Rood, Johannes J.; Claas, Frans H.J.

doi:10.1016/j.jri.2009.05.003

« Previous Next »Journal of Reproductive Immunology
Volume 82, Issue 2 , Pages 148-157, November 2009

Fetal–maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells

Tamara Tilburgs
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
- Department of Obstetrics, Leiden University Medical Center, The Netherlands
- Corresponding author at: Department of Immunohematology and Blood Transfusion, E3Q, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 0 71 5263362; fax: +31 0 71 5265267.
Sicco A. Scherjon
- Department of Obstetrics, Leiden University Medical Center, The Netherlands
Barbara J. van der Mast
- Department of Obstetrics, Leiden University Medical Center, The Netherlands
Geert W. Haasnoot
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
Minke Versteeg-v.d.Voort-Maarschalk
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
Dave L. Roelen
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
Johannes J. van Rood
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
Frans H.J. Claas
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands

Received 12 December 2008; received in revised form 11 March 2009; accepted 1 May 2009. published online 13 July 2009.

Abstract

Human leukocyte antigen-C (HLA-C) is the only polymorphic classical histocompatibility antigen expressed by fetal trophoblasts at the fetal–maternal interface. Interactions between HLA-C and decidual natural killer (NK) cells may facilitate trophoblast invasion into maternal tissue. Thus far no evidence has been provided that decidual T cells specifically recognize and respond to fetal alloantigens at the fetal–maternal interface. In this study, we show that pregnancies containing a HLA-C mismatched child induce an increased percentage of CD4⁺CD25^dim activated T cells in decidual tissue. In addition, HLA-C mismatched pregnancies exhibit a decidual lymphocyte response to fetal cells and contain functional CD4⁺CD25^bright regulatory T cells in decidual tissue, whereas HLA-C matched pregnancies do not. This suggests that decidual T cells specifically recognize fetal HLA-C at the fetal–maternal interface but are prevented from inducing a destructive immune response in uncomplicated pregnancies.

Abbreviations: Treg, regulatory T cell, Tact, activated T cell, TCR, T cell receptor, KIR, killer cell immunoglobulin-like receptor, cPBL, control peripheral blood lymphocyte, mPBL, maternal peripheral blood lymphocyte, UCB, umbilical cord blood, S.I., Suppression Index