Persistence of decidual NK cells and KIR genotypes in healthy pregnant and preeclamptic women: a case-control study in the third trimester of gestation.
BACKGROUND
Natural Killer (NK) cells are the most abundant lymphocytes in the decidua during early gestation. The interactions of NK cells with the extravillous cytotrophoblast have been associated with a normal spiral artery remodeling process, an essential event for a successful pregnancy. Recent data indicate that alterations in the amount of decidual NK (dNK) cells contribute to the development of preeclampsia (PE). Moreover, genetic studies suggest that Killer Immunoglobulin-like Receptors (KIR) expressed in dNK cells influence the susceptibility to PE. Although dNK cells have been well characterized during early pregnancy, they have been scarcely studied in the third trimester of gestation. The aim of this work was to characterize dNK cells at the last trimester of gestation and to analyze the KIR genotype of healthy and PE women.


METHODS
Decidual samples were obtained during Caesarean section from control (n = 10) and PE (n = 9) women. Flow cytometric analysis of CD3, CD56, CD16 and CD9 was used to characterize and quantify dNK cells in both groups. Cell surface markers from decidual leukocytes were compared with PBMC from healthy donors.KIR genotyping was performed in genomic DNA (control, n = 86; PE, n = 90) using PCR-SSP.


RESULTS
The results indicate that dNK cells persist throughout pregnancy. They represented 20% of total leukocytes in control and PE groups, and they expressed the same cell surface markers (CD3-, CD56+, CD16- and CD9+) as dNK in the first trimester of gestation. There were no significant differences in the percentage of dNK cells between control and PE groups. The analysis of KIR gene frequencies and genotypes was not statistically different between control and PE groups. The ratio of activating to inhibitory genes indicated that the overall inhibitory balance (0.2-0.5) was more frequent in the PE group (control, 31.3% vs PE, 45.5%), and the activating balance (0.6-1.1) was more frequent in the control group (control, 68.6% vs PE, 54.4%). However this difference was not significant.


CONCLUSIONS
We demonstrated the persistence of dNK cells in PE and control women at the third trimester of pregnancy; these dNK cells had a similar phenotype to those found during early pregnancy. The predominance of a KIR inhibitory balance in the PE group could be associated to the physiopathology of PE.
Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México. ellysnz@yahoo.com
Elly N
EN
Sánchez-Rodríguez
Sonia
S
Nava-Salazar
C Adriana
CA
Mendoza-Rodríguez
Carlos
C
Moran
Juan F
JF
Romero-Arauz
Enrique
E
Ortega
Julio
J
Granados
Alicia
A
Cervantes-Peredo
Marco
M
Cerbón
D016022:Case-Control Studies; D003656:Decidua / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000276:immunology*; D054340:Receptors, KIR / Q000378:metabolism*
D054340:Receptors, KIR
Immunol Rev. 2001 Jun;181:20-38
11513141
Reprod Biol Endocrinol. 2009 Nov 23;7:132
19930648
Reproduction. 2006 Jan;131(1):175-82
16388020
Hum Reprod. 1991 Jul;6(6):791-8
1757516
Eur J Obstet Gynecol Reprod Biol. 2003 Jul 1;109(1):8-15
12818436
Reproduction. 2009 Jul;138(1):177-84
19357130
J Reprod Immunol. 2004 Jun;62(1-2):125-37
15288188
Placenta. 2008 Mar;29 Suppl A:S60-6
18039547
Virchows Arch. 2006 Mar;448(3):269-76
16328353
Am J Reprod Immunol. 1993 Apr;29(3):135-40
7690570
Hum Immunol. 2006 Jan-Feb;67(1-2):85-93
16698429
J Exp Med. 2002 Jan 21;195(2):277-82
11805154
Mediators Inflamm. 2002 Apr;11(2):105-11
12061422
Am J Pathol. 2009 May;174(5):1959-71
19349361
Tissue Antigens. 2004 Sep;64(3):235-42
15304003
Nat Rev Immunol. 2002 Sep;2(9):656-63
12209134
J Reprod Immunol. 2009 Oct;82(1):24-31
19732959
Placenta. 2003 Apr;24 Suppl A:S21-7
12842410
J Reprod Immunol. 1993 Jan;23(1):41-9
8429523
Obstet Gynecol. 2002 Jan;99(1):159-67
16175681
Eur J Immunol. 2005 Oct;35(10):3054-63
16134082
Curr Top Microbiol Immunol. 2006;298:225-57
16329188
Clin Exp Immunol. 2007 Jul;149(1):139-45
17459078
Annu Rev Genomics Hum Genet. 2006;7:277-300
16824023
J Exp Med. 2004 Oct 18;200(8):957-65
15477349
J Immunol. 2008 Jul 1;181(1):39-46
18566368
J Reprod Immunol. 2006 Jun;70(1-2):93-8
16427138
Mol Hum Reprod. 1999 Feb;5(2):162-7
10065872
Clin Immunol. 2007 Jul;124(1):69-76
17524808
Am J Reprod Immunol Microbiol. 1987 Sep;15(1):1-8
2892429
Am J Reprod Immunol. 2006 Nov-Dec;56(5-6):275-85
17076671
Placenta. 2006 Sep-Oct;27(9-10):939-58
16490251
J Reprod Immunol. 1996 Aug;31(1-2):109-23
8887126
J Exp Med. 2003 Oct 20;198(8):1201-12
14568979
Hum Reprod. 1997 Nov;12(11):2393-8
9436671
Tissue Antigens. 2007 Apr;69 Suppl 1:112-3
17445181
J Reprod Immunol. 2009 Jun;80(1-2):22-32
19394706
Immunol Today. 1991 Dec;12(12):432-5
1786078
Nat Med. 2006 Sep;12(9):1065-74
16892062
Hum Reprod Update. 1998 Sep-Oct;4(5):480-5
10027599
Eur J Immunol. 2008 Nov;38(11):2948-51
18979515
Virchows Arch. 1999 Mar;434(3):207-11
10190299
Tissue Antigens. 2007 Apr;69 Suppl 1:125-9
17445185