Therapy with Dendritic Cells Influences the Spontaneous Resorption Rate in the CBA/J × DBA/2J Mouse Model

Blois, Sandra M.; Soto, Catalina Dirney Alba; Olmos, Sofı́a; Chuluyan, Eduardo; Gentile, Teresa; Arck, Petra C.; Margni, Ricardo A.

doi:10.1046/j.8755-8920.2003.00120.x

Cited by 44 publications

(43 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interpretation that GM-CSF facilitates an appropriate T cell response to pregnancy is consistent with experiments showing that administration of exogenous GM-CSF in the preimplantation period can normalize fetal loss rates in abortion-prone CBA 3 DBA/2 mice and is associated with expansion of CD8 + T cells with suppressive function (68). Administration of bone marrow-derived DCs from normal fertile mice to abortion-prone CBA 3 DBA/2 mice similarly reduces the miscarriage rate, implying that GM-CSF-mediated rescue of fetal loss is operating through a DC-mediated mechanism (69).…”

Section: Cd11cmentioning

confidence: 93%

GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

Moldenhauer

Keenihan

Hayball

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Uterine dendritic cells (DCs) are critical for activating the T cell response mediating maternal immune tolerance of the semiallogeneicfetus. GM-CSF (CSF2), a known regulator of DCs, is synthesized by uterine epithelial cells during induction of tolerance in early pregnancy. To investigate the role of GM-CSF in regulating uterine DCs and macrophages, Csf2-null mutant and wild-type mice were evaluated at estrus, and in the periconceptual and peri-implantation periods. Immunohistochemistry showed no effect of GM-CSF deficiency on numbers of uterine CD11c+ cells and F4/80+ macrophages at estrus or on days 0.5 and 3.5 postcoitum, but MHC class II+ and class A scavenger receptor+ cells were fewer. Flow cytometry revealed reduced CD80 and CD86 expression by uterine CD11c+ cells and reduced MHC class II in both CD11c+ and F4/80+ cells from GM-CSF–deficient mice. CD80 and CD86 were induced in Csf2−/− uterine CD11c+ cells by culture with GM-CSF. Substantially reduced ability to activate both CD4+ and CD8+ T cells in vivo was evident after delivery of OVA Ag by mating with Act-mOVA males or transcervical administration of OVA peptides. This study shows that GM-CSF regulates the efficiency with which uterine DCs and macrophages activate T cells, and it is essential for optimal MHC class II- and class I-mediated indirect presentation of reproductive Ags. Insufficient GM-CSF may impair generation of T cell-mediated immune tolerance at the outset of pregnancy and may contribute to the altered DC profile and dysregulated T cell tolerance evident in infertility, miscarriage, and preeclampsia.

show abstract

Section: Cd11cmentioning

confidence: 93%

GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

Moldenhauer

Keenihan

Hayball

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Kammerer et al described the presence of subpopulations of DC in decidual tissue during the early phase of human pregnancy which seem to participate in the protection of the allogeneic fetus in a mouse pregnancy model. [81][82][83] Using in vitro models we could oberve that those DC differentiated from CD14C cells from fertile women and co-cultured with trophoblast cells prevented the up-regulation of CD83 expression, a maturation marker after a challenged with LPS. 84 In fact, they did not modulate the expression of CD86, CD40 and HLA-DR suggesting that DCs remained in a semi-mature state.…”

Section: Differential Migration and Activation Profile Of Dendritic Cmentioning

confidence: 99%

“…In fact, CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. 82 Endometrial stromal cells under the decidualization program differentiate into epithelioid decidual cells and secrete diverse mediators, contributing to the generation of a local immune response supporting the nidation of a semiallogenic fetus. 83,84 Using an in vitro model of decidualization with a human endometrial stromal cell line (HESC) stimulated with P4 and LPS simulating the inflammatory response during implantation, we observed that P4 increased VIP intracellular production in a concentration dependent manner.…”

Section: Induction and Migration Of Maternal Tregs Cellsmentioning

confidence: 99%

Decoding the chemokine network that links leukocytes with decidual cells and the trophoblast during early implantation

Ramhorst

Grasso

Paparini

et al. 2016

Cell Adhesion & Migration

View full text Add to dashboard Cite

Chemokine network is central to the innate and adaptive immunity and entails a variety of proteins and membrane receptors that control physiological processes such as wound healing, angiogenesis, embryo growth and development. During early pregnancy, the chemokine network coordinates not only the recruitment of different leukocyte populations to generate the maternalplacental interface, but also constitutes an additional checkpoint for tissue homeostasis maintenance. The normal switch from a pro-inflammatory to an anti-inflammatory predominant microenvironment characteristic of the post-implantation stage requires redundant immune tolerance circuits triggered by key master regulators. In this review we will focus on the recruitment and conditioning of maternal immune cells to the uterus at the early implantation period with special interest on high plasticity macrophages and dendritic cells and their ability to induce regulatory T cells. We will also point to putative immunomodulatory polypeptides involved in immune homeostasis maintenance at the maternal-placental interface.

show abstract

“…25 Mouse BM-derived DCs (BMDCs) were obtained from C57Bl/6J femurs and tibias and cultured in IMDM (GIBCO-BRL) containing 10% FCS and 30% GM-CSF-containing J558 conditioned medium, prepared as described previously. 26 BMDCs were routinely checked for purity and maturation markers by flow cytometry. OT-1 CD8 ϩ T cells were isolated from lymph node and spleen suspensions of OT-1 mice.…”

Section: Cellsmentioning

confidence: 99%

Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity

Tacken

Zeelenberg

Cruz

et al. 2011

Blood

160

132

View full text Add to dashboard Cite

Effective vaccines consist of 2 components: immunodominant antigens and effective adjuvants. Whereas it has been demonstrated that targeted delivery of antigens to dendritic cells (DCs) improves vaccine efficacy, we report here that co-targeting of TLR ligands (TLRLs) to DCs strongly enhances adjuvanticity and immunity. We encapsulated ligands for intracellular TLRs within biodegradable nanoparticles coated with Abs recognizing DC-specific receptors. Targeted delivery of TLRLs to human DCs enhanced the maturation and production of immune stimulatory cytokines and the Ag-specific activation of naive CD8 ؉ T cells. In vivo studies demonstrated that nanoparticles carrying Ag induced cytotoxic T-lymphocyte responses at 100-fold lower adjuvant dose when TLRLs were co-encapsulated instead of administered in soluble form. Moreover, the efficacy of these targeted TLRLs reduced the serum cytokine storm and related toxicity that is associated with administration of soluble TLRLs. We conclude that the targeted delivery of adjuvants may improve the efficacy and safety of DC-based vaccines. (Blood. 2011;118(26):6836-6844) IntroductionMost vaccines currently on the market are based on the induction of long-lived Ab responses. A major challenge is the generation of vaccines that, next to Abs, also induce Ag-specific killing of pathogen-infected cells or tumor cells by cytotoxic T lymphocytes (CTLs). This might open new opportunities for the treatment of cancer or persistent viral infections, for which induction of strong cellular immunity seems to be essential. 1 Dendritic cells (DCs) are professional APCs that play a key role in regulating adaptive immunity, and both preclinical and clinical studies have exploited DCs in an attempt to induce antiviral or antitumor CTL responses. Most of these studies explored ex vivo Ag loading of autologous monocyte-derived DCs that were readministered to the patient, a laborious and costly procedure. The discovery of pattern recognition receptors, such as C-type lectin receptors (CLRs) that mediate Ag uptake, allow for a more direct strategy by targeting Ags to DCs in vivo. Some of these CLRs are restricted to APCs, such as macrophages or DCs. Therefore, targeted delivery exploiting CLRs has already been demonstrated to enhance Ag presentation and results in immunity when DC maturation stimuli such as TLR ligands (TLRLs) are co-administered. 2 TLRs constitute a family of pattern recognition receptors that recognize pathogen-associated molecular patterns and trigger immune cell activation. Consequently, natural TLRLs and their mimetics are increasingly being applied in immunotherapeutic strategies. 3 TLRLs are potent inducers of innate immune responses and have been evaluated as monotherapies to treat infection and cancer. 4,5 In addition, TLRLs have been applied as adjuvants to stimulate adaptive immune responses. 3 We hypothesized that targeted delivery of both Ag and TLRLs directly to DCs may greatly enhance immune responses. This approach would guarantee that the APCs that take up Ag are...

show abstract

Therapy with Dendritic Cells Influences the Spontaneous Resorption Rate in the CBA/J × DBA/2J Mouse Model

Abstract: Syngeneic DC prevented abortions and this was linked to a decrease in IL-6 levels, but not with levels of asymmetric antibodies.

Cited by 44 publications

References 45 publications

GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

Decoding the chemokine network that links leukocytes with decidual cells and the trophoblast during early implantation

Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity

Contact Info

Product

Resources

About