Maternal Th1- and Th2-Type Reactivity to Placental Antigens in Normal Human Pregnancy and Unexplained Recurrent Spontaneous Abortions

Raghupathy, Raj; Makhseed, M.; Azizieh, Fawaz; Hassan, Naheda; Al-Azemi, Majedah; Al-Shamali, Eman

doi:10.1006/cimm.1999.1532

Cited by 317 publications

(223 citation statements)

References 51 publications

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“…None of the women were on medications other than multivitamins. We have previously demonstrated higher production of the Th1 type cytokine IFN-␥ and lower production of the Th2 cytokine IL-10 by PBMCs in a subgroup of women with unexplained RPL; 5,6 while less than 3% of fertile women have had a positive IFN-␥ response in our assay system. Based on PBMC IFN-␥ production to trophoblast antigen challenge, we divided women with RPL into Th1(+) and Th1(−) subgroups which were similar in age (range: 24-42 years) and number of prior losses (mean 3.873, range 3-11 for Th1(+) groups and mean 3.95, range 3-7 for Th1(−) groups).…”

mentioning

confidence: 64%

“…1,2 Recent studies in rodents provided evidence indicating that predominant T helper 2 (Th2)-type cytokine production at the fetalmaternal interface is associated with successful gestation; while Th1-type immunity is incompatible with pregnancy success. 3,4 Studies in women have suggested that Th1-type immunity to trophoblast antigens 5,6 and defective Th2 cytokine production by decidual T cells are associated with RPL. 7 Th1-type immunity may contribute to reproductive failure, since Th1 cytokines such as interferon-gamma (IFN-␥) and tumor necrosis factor-alpha (TNF-␣) have been demonstrated to disrupt a number of reproductive process in vitro.…”

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confidence: 99%

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T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region

et al. 2002

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Recurrent pregnancy loss (RPL) is a common disorder during early gestation. Recent evidence suggests that T helper 1 (Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RPL of otherwise unknown etiology, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-1 may influence Th1/Th2 immune responsiveness and has been implicated in the establishment of successful pregnancy. In the present study, we investigated polymorphism of the IL-1␤ gene (IL1B) in women with a history of RPL. Significant increases in the frequencies of IL1B promoter region variants IL1-511C and IL1B-31T were found in women with a history of RPL. Increased frequencies of these two variants and their homozygotes were found only in cases having evidence of Th1 immunity to trophoblast as determined by IFN-␥ production of peripheral blood mononuclear cells (PBMCs) stimulated with a trophoblast cell-line extract. Significantly higher IFN-␥ production by PBMCs in response to trophoblast correlated with variant IL1B-511C and its homozygocity in women with RPL. These results suggest that variants −511C and −31T in the IL1B promoter region confer risk for RPL associated with Th1 immunity to trophoblast antigens.

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confidence: 64%

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confidence: 99%

T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region

et al. 2002

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“…Significantly higher serum levels of the Th1 cytokine IFN-γ have been detected in women with unexplained recurrent spontaneous abortions (Raghupathy et al, 1999). Several similar studies indicate increased Th1-like and decreased Th2-like responses among women with pregnancy losses, whereas women with successful pregnancies tend to have an increased Th2-like response Makhseed et al, 2000;Makhseed et al, 2001;Kwak-Kim et al, 2003).…”

Section: Introductionmentioning

confidence: 96%

Increased circulating paternal antigen-specific IFN-γ- and IL-4-secreting cells during pregnancy in allergic and non-allergic women

Persson

Ekerfelt

Ernerudh

et al. 2008

Journal of Reproductive Immunology

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“…Th1/Th2 cytokine balance with Th2 predominance has been seen as a very important mechanism determining the survival of the fetus in the maternal uterus [6][7][8][9][10][11][12][13][14][15][16][17]. However, mice genetically deficient for IL-4 and IL-10 do not show disturbed pregnancy [18], suggesting that Th2 cells are not essential for normal pregnancy and alloreactive Th1 cells must be differently regulated, as already proposed [19][20][21].…”

Section: Introductionmentioning

confidence: 97%

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

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The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-c and TNF-a were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-b and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

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Maternal Th1- and Th2-Type Reactivity to Placental Antigens in Normal Human Pregnancy and Unexplained Recurrent Spontaneous Abortions

Cited by 317 publications

References 51 publications

T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region

T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region

Increased circulating paternal antigen-specific IFN-γ- and IL-4-secreting cells during pregnancy in allergic and non-allergic women

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

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