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International Immunology Advance Access originally published online on January 29, 2008
International Immunology 2008 20(3):405-412; doi:10.1093/intimm/dxn001
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Role of human non-invariant NKT lymphocytes in the maintenance of type 2 T helper environment during pregnancy

Yasushi Uemura1,*, Motoharu Suzuki2,*, Tian-Yi Liu1,*, Yayoi Narita1, Shinya Hirata3, Hideki Ohyama4, Osamu Ishihara2 and Sho Matsushita1

1 Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama 350-0495, Japan
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama 350-0495, Japan
3 Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
4 Department of Pathology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan

Correspondence to: Y. Uemura; E-mail: uemura{at}saitama-med.ac.jp

The molecular and cellular mechanisms that generate the Th2 cytokine environment necessary for the maintenance of pregnancy are still not fully understood. We herein show that the human decidua is highly enriched for TCR{alpha}β+CD161+ NKT cells. They express non-invariant antigen receptors encoded by diverse TCRV{alpha}- and Vβ-chain gene segments, thereby referred to as non-invariant NKT (non-iNKT) cells. In spite of their diverse TCR expression, they do not recognize fetal allo-antigens but specifically responded to CD1d-transfected cell lines. In contrast to the peripheral blood non-iNKT cells, the decidua-residing non-iNKT cells had a marked Th2 bias. In addition, they suppress the mixed leukocyte reaction directed against the paternal antigens. The Th2 cytokines have been known to stimulate trophoblast outgrowth and invasion. Thereby, the non-iNKT cells residing in the decidual tissue may have a functionally important interaction with the villous and extravillous trophoblast cells expressing CD1d and may therefore play a pivotal role in successful pregnancy by inhibiting fetal rejection and enhancing placental growth. These findings may reflect one mechanism that is an essential component for the Th2 environment necessary for the maintenance of pregnancy.

Keywords: CD1, human, NKT cells, pregnancy

* These authors contributed equally to this study.

Transmitting editor: K. Okumura

Received 17 September 2007, accepted 28 December 2007.


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