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

Miwa, Naoko; Hayakawa, Satoshi; Miyazaki, Satomi; Myojo, Subaru; Sasaki, Yasushi; Sakai, Masatoshi; Takikawa, Osamu; Saito, Shigeru

doi:10.1093/molehr/gah246

Cited by 164 publications

(151 citation statements)

References 27 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…The direct effect of abatacept binding to CD80/86 on APCs remains a topic of controversy (37,38,(48)(49)(50). While some studies have demonstrated that CTLA-4Ig induced the up-regulation of IDO in DCs, which subsequently modulated T cell activation, our data and other transcriptional data have failed to confirm this (37,38).…”

Section: Discussioncontrasting

confidence: 59%

Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells

Patakas

Weir

et al. 2016

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. To determine at the phenotypic, functional, and transcriptional levels whether abatacept, a CTLA-4Ig molecule that binds with high affinity to CD80/86 on antigen-presenting cells (APCs) and is used to treat rheumatoid arthritis, induces a state of immunologic tolerance in T cells and dendritic cells in mice.Methods. We investigated the capacity of abatacept to regulate the development of antigen-specific immunologic tolerance in vivo using murine models of priming and tolerance to generate highly purified antigen-specific T cell populations and CD11c1 APCs. These were combined with detailed immunologic and full genome transcriptional analyses.Results. We found that abatacept inhibited T cell activation, but did not render T cells anergic or lead to the generation of Treg cells. However, it induced a sustained inhibition of T cell activation due to the inability of these cells to progress through the cell cycle following T cell receptor stimulation. We also observed that this state was accompanied by an inhibition of dendritic cell activation due to their reduced licensing by T cells.Conclusion. This study provides detailed insight into the mode of action of abatacept, demonstrating that its effectiveness is not due to the induction of T cell tolerance, but rather to a sustained inhibition of T cell activation that results in reduced functionality of APCs, with significant implications for its clinical application.

show abstract

Section: Discussioncontrasting

confidence: 59%

Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells

Patakas

Weir

et al. 2016

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…Reflecting remarkable plasticity, CD14 1 myelomonocytic cells efficiently respond to various environmental stimuli, particularly the semi-allograft, which might induce the differentiation of these cells in a tissue-specific manner for immune regulation and host defense responses 2,[27][28][29] . Studies have shown that CD14 1 myelomonocytic cells, which intimately contact the embryo allograft, displayed a unique ability to promote immunotolerance via the induction of Tregs 2 .…”

Section: Discussionmentioning

confidence: 99%

Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Zhang

Sun

et al. 2015

Cell Mol Immunol

View full text Add to dashboard Cite

Successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Myeloid-derived suppressor cells (MDSCs), which are capable of inhibiting T-cell responses, are highly increased in the early stages of pregnancy. Although recent reports indicate a role for MDSCs in fetal-maternal tolerance, little is known about the expansion of MDSCs during pregnancy. In the present study, we demonstrated that the trophoblast cell line HTR8/SVneo could instruct peripheral CD14 1 myelomonocytic cells toward a novel subpopulation of MDSCs, denoted as CD14 1 HLA-DR 2/low cells, with suppressive activity and increased expression of IDO1, ARG-1, and COX2. After interaction with HTR8/SVneo cells, CD14 1 myelomonocytic cells secrete high levels of CCL2, promoting the expression of signal transducer and activator of transcription 3. We utilized a neutralizing monoclonal antibody to reveal the prominent role of CCL2 in the induction of CD14 1 HLA-DR 2/low MDSCs. In combination, the results of the present study support a novel role for the cross-talk between the trophoblast cell line HTR8/SVneo and maternal CD14 1 myelomonocytic cells in initiating MDSCs induction, prompting a tolerogenic immune response to ensure a successful pregnancy. Cellular & Molecular Immunology

show abstract

“…23,44 In humans, however, CTLA-4 expressed in Treg cells up-regulates IDO expression on decidual and peripheral blood DC and monocytes by the induction of IFN-c production. 45 Decidual Treg seem to work by cell-cell contact 46 and suppression of Tcell responses. 47 Dr. Saito extensively revises the type of Treg present during pregnancy and discusses the importance of correctly identifying their phenotypes for future clinical applications.…”

Section: Tafurimentioning

confidence: 99%

Adaptive Immune Responses During Pregnancy

Zenclussen

2013

American J Rep Immunol

View full text Add to dashboard Cite

It has long been believed that there is no immune interaction between mother and conceptus during pregnancy. This concept changed after evidence was provided that the maternal immune system is aware of the semiallogeneic conceptus and develops strategies to tolerate it. Since then, finely regulated mechanisms of active tolerance toward the fetus have been described. This Special Issue of the American Journal of Reproductive Immunology deals with these mechanisms. It begins with the description of minor histocompatibility antigens in the placenta; it further goes through adaptive immune responses toward paternal fetal antigens, mostly concentrating on regulatory T cells and molecules modulating the Th1/Th2 balance. The participation of antibody‐producing B cells in normal and pathological pregnancies is also discussed. This introductory chapter resumes the concepts presented throughout the Issue and discusses the clinical applications raised from these concepts.

show abstract

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

Cited by 164 publications

References 27 publications

Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells

Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells

Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Adaptive Immune Responses During Pregnancy

Contact Info

Product

Resources

About