Non-inherited maternal antigens, pregnancy, and allotolerance

Bracamonte‐Baran, William; Burlingham, William J.

doi:10.4103/2319-4170.143498

Cited by 25 publications

(36 citation statements)

References 68 publications

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“…It is clear that CBP has immunosuppressive properties but the mechanisms by which fetal immune cells may recognise maternal antigens causing pathology is less clear and described in detail in a recent review . It is also possible that the unusual expression pattern of class I molecules on placental tissues may elicit fetal NK cell responses against its own placenta, a situation that would be incompatible with continuing pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity

et al. 2015

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NK cells play a key role in innate elimination of virally infected or neoplastic cells but they can be circumvented by immunoevasive mechanisms enabling viral spread or tumor progression. Engagement of the NKG2D activating receptor with soluble forms of itsligand is one such mechanism of inducing NK cell hyporesponsiveness. Interestingly, this immunoevasive strategy among others is described at the maternal-fetal interface where tolerance of the semi-allogeneic fetus is required to allow successful human pregnancy. Understanding of maternal-fetal tolerance is increasing but mechanisms preventing alloreactivity of fetal immune cells against the maternal host are less well understood. The study of umbilical cord blood has enabled insight of the fetal immune system, which appears immature and inert. We have found that soluble NKG2D ligands (sNKG2DLs) are present in cord blood plasma (CBP) and associate with adult NK cell hyporesponsiveness demonstrated by reduced CD107a expression and secretion of IFN-γ upon stimulation. The capacity of NK cells to kill K562 cells or proliferate was also reduced by incubation with CBP; however, physical removal of sNKG2DL from CBP restored K562 lytic function and NKG2D expression. Therefore, our results strongly suggest sNKG2DLs are expressed in CBP as a mechanism of fetal-maternal tolerance in human pregnancy. Keywords:Ligand r NK cell r NKG2D r Pregnancy r Tolerance Additional supporting information may be found in the online version of this article at the publisher's web-site Eur. J. Immunol. 2015Immunol. . 45: 2324Immunol. -2334 Innate immunity 2325 group 2, member D receptor (NKG2D) on infected and tumor cells [4,5]. NKG2D is a C-type lectin-like molecule and interaction with its cognate ligand expressed on stressed cells results in direct cytolysis and cytokine production [6]. Immunoevasive strategies allow some viruses and tumors to escape detection by intracellular retention of NKG2D ligands (NKG2DLs) [7]. Alternatively, soluble NKG2DLs (sNKG2DLs) can be released from the cell surface as free-soluble molecules by protease cleavage or by secretion on exosomes [5]. NKG2D is expressed on NKT cells, γδ + T cells and CD8 + T cells as well as NK cells. Interaction with sNKG2DLs leads to downregulation of this receptor, rendering the cell hyporesponsive [8,9]. There are eight known types of NKG2DLs that divide into two groups; [10,11] the highly polymorphic MHC class Irelated chain A and B (MICA/B) and the unique long 16 binding proteins (ULBP1-6), which are also polymorphic [12][13][14][15]. It is probable that viral and possibly tumor immunity has shaped evolution of NKG2DLs in an effort to combat immunoevasive strategies targeting NKG2D. Human pregnancy presents a unique immunological dilemma as the fetus is semiallogeneic and a potential target for destruction by maternal T cells recognizing paternal antigens on placental trophoblast cells [16]. Maternal T-cell responses against trophoblasts are limited by unusual expression of MHC class I antigens by the various trophoblast...

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Section: Discussionmentioning

confidence: 99%

Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity

et al. 2015

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“…Development of autoimmune diseases is a consequence of lack of self-tolerance, which can arise due to defective function of any of the features contributing to the unresponsive status of the immune system toward self-antigens, i.e., anergy, regulation, and clonal deletion [1, 2]. Autoimmunity requires a self-specific response, despite the fact that innate response might be involved.…”

Section: 1 Myocarditismentioning

confidence: 99%

“…This genetic variability has functional consequences in terms of the affinity of MHC molecules for specific peptides. Despite MHC molecules being promiscuous in terms of peptide presentation, certain biases exist as consequence of the avidity and affinity of MHC molecules for specific peptides [2]. …”

Section: 3 Specific Factors Triggering/predisposing Myocarditis Dementioning

confidence: 99%

Cardiac Autoimmunity: Myocarditis

Bracamonte‐Baran

Čiháková

2017

Advances in Experimental Medicine and Biology

Self Cite

174

170

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“…On the other hand, the indirect pathway requires a host APC to engulf and process allogeneic antigens and express them on self‐MHC‐II molecules for recognition by effector CD4 T cells . From this, one can deduce that a T cell clone with ‘direct’ specificity will only interact with a donor APC expressing allo‐MHC, while an ‘indirect’ T cell will only interact with a host APC expressing alloantigenic peptides on self‐MHC . Thus, according to this paradigm, each T cell requires a specific APC with no possibility of a single APC priming direct and indirect T cells (for major antigens).…”

Section: Exosomes In Tolerance and Transplant Rejectionmentioning

confidence: 99%

Role of exosomes in tumour and transplant immune regulation

Lema

Burlingham

2019

Scand J Immunol

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Exosomes are a potent means for intercellular communication. However, exosomes have received intensive research focus in immunobiology only relatively recently.Because they transport proteins, lipids and genetic material between cells, they are especially suited to amplify their parental cell's message and overcome the physical constraints of cell-to-cell contact, that is exosome release gives cells the ability to alter distant, non-contiguous cells. As progress is made in this field, it has become increasingly obvious that exosomes are involved in most biological processes. In the immune system, exosomes are fundamental tools used by every immune cell type to fulfil its function and promote inflammation or tolerance. In this review, we first summarize key aspects of immune cell-specific exosomes and their functions. Then, we describe how exosomes have been shown to be indispensable orchestrators of the immune response in two immunological scenarios, namely transplant rejection or tolerance, and tumour evasion or initiation of anti-tumour immune responses.

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Non-inherited maternal antigens, pregnancy, and allotolerance

Cited by 25 publications

References 68 publications

Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity

Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity

Cardiac Autoimmunity: Myocarditis

Role of exosomes in tumour and transplant immune regulation

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