Nonhuman primate placental MHC expression: a model for exploring mechanisms of human Maternal-Fetal immune tolerance

Golos, Thaddeus G.

doi:10.1016/j.humimm.2003.08.349

Cited by 9 publications

(8 citation statements)

References 42 publications

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“…Paan-AG1 protein expression was similar to that of Paan-AG5 while Paan-AG2 protein was not detected in these tissues [49]. Similar results were obtained from analysis of the rhesus monkey counterpart, Mamu-AG[48,50]. These properties are similar to those observed in HLA-G, as summarized in Table 2.…”

Section: Paan-ag: Studies On Protein Expression and Gene Regulationsupporting

confidence: 67%

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The role of HLA-G in human pregnancy

Hunt

Langat

McIntire

et al. 2006

Reprod Biol Endocrinol

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Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy.

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Section: Paan-ag: Studies On Protein Expression and Gene Regulationsupporting

confidence: 67%

“…Despite the similarity to the HLA-A locus, the messages and proteins encoded by this gene are strikingly similar to those of the HLA-G locus (reviewed in Ref. [45,50]), leading to the hypothesis that the AG locus may be the functional homologue of HLA-G in these species.…”

Section: Paan-ag: Studies On Protein Expression and Gene Regulationmentioning

confidence: 99%

The role of HLA-G in human pregnancy

Hunt

Langat

McIntire

et al. 2006

Reprod Biol Endocrinol

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“…Regulatory mechanisms may include inhibitory receptors on lymphocytes that bind ligands on fetal cells [5,54] and suppression of T lymphocytes by tryptophan catabolism via indoleamine-2,3-dioxygenase activity [55]. An alternate and nonexclusive view is that interactions of fetal cells with immune cells at the maternal–fetal interface play a role in proper implantation by shaping vascular adaptations of the surrounding maternal tissue via cytokine secretion [25,56]. Uterine tissue in early human pregnancy is characterized by extensive vascular remodeling, by invasion of HLA-G–expressing trophoblast cells, and by an abundance of maternal NK cells.…”

Section: Discussionmentioning

confidence: 99%

Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G

et al. 2005

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Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct from those generated at the plasma membrane. The activity of natural killer (NK) cells, which are important effectors of innate immunity and regulators of adaptive immunity, is controlled primarily by receptors that are at the cell surface. Here we show that cytokine secretion by resting human NK cells is induced by soluble, but not solid-phase, antibodies to the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was endocytosed into KIR2DL4–containing compartments in NK cells and in 293T cells transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection into 293T cells occurred only with recombinant forms of KIR2DL4 that trafficked to endosomes. The profile of genes up-regulated by KIR2DL4 engagement on resting NK cells revealed a proinflammatory/proangiogenic response. Soluble HLA-G induced secretion of a similar set of cytokines and chemokines. This unique stimulation of resting NK cells by soluble HLA-G, which is endocytosed by KIR2DL4, implies that NK cells may provide useful functions at sites of HLA-G expression, such as promotion of vascularization in maternal decidua during early pregnancy.

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“…Unexpectedly, we found in the rhesus that Mamu-G is a pseudogene (Boyson et al ., 1996). However, we have defined the placental expression of a novel MHC class I locus, Mamu-AG, which shares a number of features of HLA-G (Golos, 2003; Boyson et al ., 1997). These include alternative splicing (Boyson et al ., 1997; Ryan et al ., 2002), and the expression of a soluble isoform (Ryan et al ., 2002) low polymorphism and a truncated cytoplasmic domain (Boyson et al ., 1997), and a distinctive expression pattern in which the highest mRNA and protein levels are found in placental trophoblasts (Slukvin et al ., 1998; Slukvin et al ., 2000; Slukvin et al ., 1999).…”

Section: Characterization Of the Rhesus Model: Placental Componentsmentioning

confidence: 99%

On the role of placental Major Histocompatibility Complex and decidual leukocytes in implantation and pregnancy success using non-human primate models

Golos¹,

Bondarenko²,

Dambaeva³

et al. 2010

Int. J. Dev. Biol.

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While there is broad agreement that interactions of the human maternal immune system with the tissues and cells of the implanting embryo are likely to be critical contributors to pregnancy success, there remains a dearth of information which directly confirms this expectation. Although animal models of reproductive function often provide opportunities for confirming such hypotheses, progress in this area has been sporadic due to limitations of traditional laboratory or agricultural animal models, such as rodents, sheep, pigs and cattle. Many of these limitations derive from divergent modes of implantation and placentation across mammalian species. Over the past decade there has been progress in the development of the nonhuman primate as a model in which to address questions of pregnancy success in the area of immunology. The purpose of this review is to compare available model species, summarize current knowledge and recent progress with an emphasis on experimental in vivo manipulations, and suggest areas available for additional study and growth.

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Nonhuman primate placental MHC expression: a model for exploring mechanisms of human Maternal-Fetal immune tolerance

Cited by 9 publications

References 42 publications

The role of HLA-G in human pregnancy

The role of HLA-G in human pregnancy

Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G

On the role of placental Major Histocompatibility Complex and decidual leukocytes in implantation and pregnancy success using non-human primate models

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