Kinetics of regulatory T cells during murine pregnancy

被引:90
作者
Thuere, Catharina
Zenclussen, Maria Laura
Schumacher, Anne
Langwisch, Stefanie
Schulte-Wrede, Ursula
Teles, Ana
Paeschke, Steffen
Volk, Hans-Dieter
Zenclussen, Ana Claudia
机构
[1] Univ Magdeburg, Univ Frauenklin Magdeburg, Fak Med,Dept Gynecol & Obstet, Reprod Immunol Expt Gynakol & Geburtshilfe Univ F, D-39108 Magdeburg, Germany
[2] Univ Med, Charite, Inst Med Immunol, Berlin, Germany
关键词
IDO; mouse; pregnancy; regulatory T cells; tolerance;
D O I
10.1111/j.1600-0897.2007.00538.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Problem The semi-allogeneic fetus is usually tolerated by the maternal immune system. This was proposed to be modulated by CD4(+)CD25(+)foxp3(+) regulatory T cells (Treg). We aimed to determine the kinetics of Treg during murine gestation and investigate whether changes in Treg levels respond to hormonal variations during pregnancy or generated changes in the local indolamine dioxygenase (IDO) expression. Method of study We included in our studies the well-known CBA/J x DBA/2J abortion-prone combination using CBA/J x BALB/c as controls. CBA/J x C57/BL6 and BALB/c x C57/BL6 were included as further controls. Animals were killed on days 0, 2, 5, 8, 10, and 12 of pregnancy to measure the levels of Treg, pregnancy-related hormones and IDO expression. Results A Treg augmentation in normal pregnancy combinations could be observed on day 2 in several organs contrary to the observations made in abortion-prone mice. No differences in hormonal levels could be seen among all groups. IDO was expressed exclusively in placenta starting from day eight, showing no variations among the groups. Conclusion Differences in Treg levels and pregnancy outcome do not correlate with changes in hormonal levels. In addition, as Treg augmentation takes place early and it is observed mainly in the decidual component of the fetal-maternal interface, IDO does not seem to be the pathway underlying Treg protective activity as proposed for humans.
引用
收藏
页码:514 / 523
页数:10
相关论文
共 19 条
[1]   Regulatory T cells mediate maternal tolerance to the fetus [J].
Aluvihare, VR ;
Kallikourdis, M ;
Betz, AG .
NATURE IMMUNOLOGY, 2004, 5 (03) :266-271
[2]   Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific [J].
Baban, B ;
Chandler, P ;
McCool, D ;
Marshall, B ;
Munn, DH ;
Mellor, AL .
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2004, 61 (02) :67-77
[3]   Asymmetric antibodies (AAb) in the female reproductive tract [J].
Blois, S ;
Zenclussen, AC ;
Roux, ME ;
Olmos, S ;
di Conza, J ;
Arck, PC ;
Margni, RA .
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2004, 64 (1-2) :31-43
[4]   Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system [J].
Erlebacher, A ;
Zhang, D ;
Parlow, AF ;
Glimcher, LH .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (01) :39-48
[5]   Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma [J].
Evans, PC ;
Lambert, N ;
Maloney, S ;
Furst, DE ;
Moore, JM ;
Nelson, JL .
BLOOD, 1999, 93 (06) :2033-2037
[6]   Natural history of fetal cell microchimerism during and following murine pregnancy [J].
Khosrotehrani, K ;
Johnson, KL ;
Guégan, S ;
Stroh, H ;
Bianchi, DW .
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2005, 66 (01) :1-12
[7]   CD25+CD4+ regulatory T cells prevent graft rejection:: CTLA-4- and IL-10-dependent immunoregulation of alloresponses [J].
Kingsley, CI ;
Karim, M ;
Bushell, AR ;
Wood, KJ .
JOURNAL OF IMMUNOLOGY, 2002, 168 (03) :1080-1086
[8]   Policing pregnancy: Tregs help keep the peace [J].
Mellor, AL ;
Munn, D .
TRENDS IN IMMUNOLOGY, 2004, 25 (11) :563-565
[9]   IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-γ increase in normal pregnancy but decrease in spontaneous abortion [J].
Miwa, N ;
Hayakawa, S ;
Miyazaki, S ;
Myojo, S ;
Sasaki, Y ;
Sakai, M ;
Takikawa, O ;
Saito, S .
MOLECULAR HUMAN REPRODUCTION, 2005, 11 (12) :865-870
[10]   Prevention of allogeneic fetal rejection by tryptophan catabolism [J].
Munn, DH ;
Zhou, M ;
Attwood, JT ;
Bondarev, I ;
Conway, SJ ;
Marshall, B ;
Brown, C ;
Mellor, AL .
SCIENCE, 1998, 281 (5380) :1191-1193