scholarly journals PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Lanfang Zhang ◽  
Chang-Qing Xia
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Ultraviolet B ◽  
Immature Dendritic Cells ◽  
Programmed Death ◽  
Induced Tolerance ◽  
Different Strains ◽  
Specific Tolerance

Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD-1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance. We first observe that the UVB-iDC-induced alloantigen-specific tolerance can be maintained for over 6 weeks. Supporting this, at 6 weeks after tolerance induction completion, alloantigen-specific tolerance is still able to be transferred to syngeneic naïve mice through adoptive transfer of CD4+ T cells. Furthermore, skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. Further studies show that PD-1/PD-L1 interaction is essential for maintaining the induced tolerance as blockade of PD-1/PD-L1 by anti-PD-L1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. Importantly, we show that PD-1/PD-L1 interaction in tolerant mice is also essential for controlling alloantigen-responding T cells, which have never experienced alloantigens. The above findings suggest that PD-1/PD-L1 plays a crucial role in maintaining immune tolerance induced by UVB-iDCs, as well as in actively controlling effector T cells specific to alloantigens.

Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4+ T cell response to β2GPI

2011 ◽  
Vol 71 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Honorio Torres-Aguilar ◽  
Miri Blank ◽  
Shaye Kivity ◽  
Mudi Misgav ◽  
Jacob Luboshitz ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Proliferative Response ◽  
Memory T Cells ◽  
Tolerance Induction ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
Tolerogenic Dendritic Cells ◽  
Specific Tolerance

ObjectivesThe importance of β2-glycoprotein I (β2GPI)-specific CD4+ T cells in the development of pathogenic processes in patients with antiphospholipid syndrome (APS) and APS mouse models is well established. Therefore, our objective is to manipulate the β2GPI specific CD4+ T cells using tolerogenic dendritic cells (tDCs) to induce tolerance. We aim to evaluate the capability of tDCs to induce antigen-specific tolerance in effector/memory T cells from patients with APS and to elucidate the involved mechanism.MethodsDCs and tDCs were produced from patients with APS peripheral-blood-monocytes, using specific cytokines. β2GPI-specific tolerance induction was investigated by coculturing control DC (cDC) or tDC, β2GPI-loaded, with autologous effector/memory T cells, evaluating the proliferative response, phenotype, cytokines secretion, viability and regulatory T cells.ResultsHuman monocyte-derived DCs treated with interleukin (IL)-10 and transforming growth factor β-1 (10/TGF-DC) induced β2GPI-specific-unresponsiveness in effector/memory CD4+ T cells (46.5%±26.0 less proliferation) in 16 of 20 analysed patients with APS, without affecting the proliferative response to an unrelated candidin. In five analysed patients, 10/TGF-DC-stimulated T cells acquired an IL-2lowinterferon γlowIL-10high cytokine profile, with just a propensity to express higher numbers of Foxp3+CTLA-4+ cells, but with an evident suppressive ability. In four of 10 analysed patients, 10/TGF-DC-stimulated T cell hyporesponsiveness could not be reverted and showed higher percentages of late apoptosis, p<0.02.ConclusionsThe inherent tolerance induction resistance of activated T cells present during the development of autoimmune diseases has delayed the application of tDC as an alternative therapy. This study highlights the 10/TGF-DC feasibility to induce antigen-specific unresponsiveness in autoreactive T cells generated in patients with APS by inducing apoptosis or T cells with regulatory abilities.

Galectin-1 Confers Endometrial Gene Expression and Protein Related to Maternal-Conceptus Immune Tolerance in Cattle

2021 ◽  
Author(s):  
Heather L Chaney ◽  
Lindsay F Grose ◽  
Jeanna M LaBarbara ◽  
Adam W Sirk ◽  
Alyssa M Blancke ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
Estrous Cycle ◽  
Immune Tolerance ◽  
Immune Suppression ◽  
Carbohydrate Binding ◽  
Expression Of Genes ◽  
Pregnant Sheep ◽  
Carbohydrate Binding Proteins

Abstract Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic CD11c+ dendritic cells, increased anti-inflammatory IL-10, and activation of FOXP3+ regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-fetal immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3 and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7 and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10 and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

scholarly journals Induced immune tolerance of autoantigen loaded immature dendritic cells in homogenic lupus mice

2014 ◽  
Vol 13 (1) ◽  
pp. 1251-1262 ◽  
Author(s):  
J. Xie ◽  
Y.K. Lin ◽  
K. Wang ◽  
B. Che ◽  
J.Q. Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Immature Dendritic Cells

scholarly journals Liver-Derived Dendritic Cells Induce Donor-Specific Hyporesponsiveness: Use of Sponge Implant as a Cell Transplant Model

2001 ◽  
Vol 10 (3) ◽  
pp. 343-350 ◽  
Author(s):  
Yang-Jen Chiang ◽  
Lina Lu ◽  
John J. Fung ◽  
Shiguang Qian
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mouse Liver ◽  
Cytotoxic T Lymphocyte ◽  
Tolerance Induction ◽  
Cell Transplant ◽  
Spleen Cells ◽  
Infiltrating Cells ◽  
Transplant Model ◽  
Ctl Activity

Spontaneously accepted mouse liver allografts are capable of protecting subsequently transplanted donor organs from rejection; however, the underlying mechanisms are unclear. Dendritic cells (DC) residing in liver grafts are likely important in tolerance induction. DC propagated from mouse liver with GM-CSF are phenotypically and functionally immature. They are poor allostimulators in MLR and prolong survival of pancreatic islet allografts. It has been problematic to perform mechanistic studies in an islet transplant model because of difficulties in obtaining sufficient graft infiltrating cells. In this study, we used a sponge allograft model [i.e., a subcutaneously implanted sponge matrix loaded with B10 (H2b) spleen cells]. To investigate the influence of administration of donor (B10) liver-derived DC on alloimmune reactivity of C3H (H2k) hosts, sponge graft infiltrating cells (SGIC) and recipient spleen cells were isolated, and their immunopheno-type and donor-specific cytotoxic T lymphocyte (CTL) activity were examined. The results illustrate that donor-specific CTL activity of T cells are lower in recipients that had received systemic treatment with liver-derived immature DC, associated with a decrease in CD8+ cell population and an increase in Gr-1+ cells in SGIC, compared with recipients treated with mature bone marrow (BM)-derived DC. Interestingly, administration of liver DC directly into the sponge did not inhibit T cell responses. These data suggest that systemic administration of donor liver DC induces donor-specific hyporesponsiveness, probably not by direct inhibition of graft infiltrating T cells. The increased Gr-1+ cells may play immune regulatory roles in induction of host donor-specific hyporesponsiveness.

scholarly journals Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Transplant Recipients ◽  
T Helper ◽  
T Helper 2 ◽  
Immature Dendritic Cells ◽  
And Migration ◽  
Mixed Lymphocyte Reactions ◽  
Dc Maturation

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.

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