Killer Ig-like receptor expression in uterine NK cells is biased toward recognition of HLA-C and alters with gestational age.
Immunogenetic studies suggest that interactions between maternal killer Ig-like receptor (KIR) expressed by uterine NK (uNK) cells, and fetal HLA-C molecules on trophoblast, influence the success of human placentation. However, the exact functional response of fresh uNK cells to trophoblast HLA-C molecules is unknown. In this study, we show by quantitative RT-PCR and FACS that both activating and inhibitory KIR specific for HLA-C are expressed at higher levels and on an increased proportion of NK cells in the human decidua compared with blood. In contrast, expression of KIR3DL1/S1, which is specific for HLA-B, is similar in both NK cell populations. Remarkably, there is also a temporal change in the expression pattern of HLA-C-specific KIR, with a decline in both intensity of expression and frequency on uNK cells throughout the first trimester of pregnancy. This selective up-regulation of KIR has functional consequences because uNK cells show increased binding of HLA-C tetramers compared with blood NK cells. Ab cross-linking shows that these KIR are functional and results in increased cytokine secretion. uNK cells, therefore, exhibit a unique KIR profile that enhances their ability to recognize trophoblast cells expressing HLA-C at the materno-fetal interface. This is the first report to demonstrate selective regulation of KIR expression over time in vivo in a normal physiological situation and suggests that KIR expression by uNK cells is regulated by the tissue microenvironment in the decidua.
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Andrew M
AM
Sharkey
Lucy
L
Gardner
Susan
S
Hiby
Lydia
L
Farrell
Richard
R
Apps
Leanne
L
Masters
Jodie
J
Goodridge
Louise
L
Lathbury
C Andrew
CA
Stewart
Sanjay
S
Verma
Ashley
A
Moffett
D003429:Cross Reactions / Q000276:immunology; D003656:Decidua / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000276:immunology; D011485:Protein Binding; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000276:immunology* / Q000378:metabolism
D015236:HLA-C Antigens; D054340:Receptors, KIR