Fetal-maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells.
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.
Tilburgs
Tamara
T
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. T.Tilburgs@LUMC.nl
Scherjon
Sicco A
SA
van der Mast
Barbara J
BJ
Haasnoot
Geert W
GW
Versteeg-V D Voort-Maarschalk
Minke
M
Roelen
Dave L
DL
van Rood
Johannes J
JJ
Claas
Frans H J
FH
D000328:Adult; D015704:CD4 Antigens / Q000096:biosynthesis; D002452:Cell Count; D049109:Cell Proliferation; D003656:Decidua / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism*; D006650:Histocompatibility Testing; D054502:Histocompatibility, Maternal-Fetal; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D011247:Pregnancy; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; D015236:HLA-C Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens