scholarly journals Origin and Biology of the Allogeneic Response

2013 ◽  
Vol 3 (8) ◽  
pp. a014993-a014993 ◽  
Author(s):  
F. G. Lakkis ◽  
R. I. Lechler
Keyword(s):  
Allogeneic Response

Identification of RANTES as a novel immunomodulator of the maternal allogeneic response

2004 ◽  
Vol 110 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Rosanna E Ramhorst ◽  
Verónica E Garcı́a ◽  
Adriana Corigliano ◽  
Gabriel A Rabinovich ◽  
Leonardo Fainboim
Keyword(s):  
Allogeneic Response

scholarly journals Suppression of the allogeneic response by the anti-allergy drugN-(3,4-dimethoxycinnamonyl) anthranilic acid results from T-cell cycle arrest

Immunology ◽  
2013 ◽  
Vol 138 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Sarah S. Zaher ◽  
David Coe ◽  
Jian-Guo Chai ◽  
Daniel F.P. Larkin ◽  
Andrew J.T. George
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Cell Cycle Arrest ◽  
Anthranilic Acid ◽  
Cycle Arrest ◽  
Allogeneic Response

scholarly journals Potential immunomodulatory role of VIP in the implantation sites of prediabetic nonobese diabetic mice

Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 733-742 ◽  
Author(s):  
Valeria Roca ◽  
Mario Calafat ◽  
Luciana Larocca ◽  
Rosanna Ramhorst ◽  
Mariana Farina ◽  
...  
Keyword(s):  
Muscle Relaxation ◽  
Embryo Implantation ◽  
Nod Mice ◽  
Exocrine Secretion ◽  
Smooth Muscle Relaxation ◽  
Nonobese Diabetic ◽  
Cytokine Balance ◽  
Implantation Sites ◽  
Nonobese Diabetic Mice ◽  
Allogeneic Response

Among several factors known to modulate embryo implantation and survival, uterine quiescence and neovascularization, maternal immunotolerance through the Th1/Th2 cytokine balance towards a Th2 profile, local regulatory T-cell (Treg) activation, and high levels of progesterone were assigned a prominent role. Vasoactive intestinal peptide (VIP) is a neuroimmunopeptide that has anti-inflammatory effects, promotes Th2 cytokines and CD4+CD25+FOXP3+Treg activation, and stimulates exocrine secretion, smooth muscle relaxation, and vasodilatation favoring uterus quiescence. The goal of the present work was to explore the participation of VIP in the implantation sites of normal and pregnant prediabetic nonobese diabetic (NOD) females, a mouse strain that spontaneously develops an autoimmune exocrinopathy similar to Sjögren's syndrome. Our results indicate a reduction in litter size from the third parturition onwards in the NOD female lifespan with increased resorption rates. Progesterone systemic levels were significantly decreased in pregnant NOD mice compared with BALB/c mice, although the allogeneic response to progesterone by spleen cells was not impaired. VIP receptors,Vipr1andVipr2(Vpac1andVpac2), were expressed at the implantation sites and VIP induced leukemia inhibitory factor (LIF) and Treg marker expression in both strains; however, a reducedVipexpression was found in NOD implantation sites. We conclude that the reduced birth rate at 16-week-old NOD mice with a Th1 systemic cytokine profile involves resorption processes with a lower expression of VIP at the sites of implantation, which acts as a local inducer of pro-implantatory LIF and Treg activation.

DOCK8-Deficient Mice Reveal a Crucial Role for Dendritic Cell Activity in the Initiation of the Allogeneic Response to Transfused Red Blood Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 658-658
Author(s):  
Stephanie C. Eisenbarth ◽  
Jeanne E. Hendrickson ◽  
Samuele Calabro ◽  
Antonia Gallman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Allogeneic Response ◽  
Deficient Mice

Abstract The generation of antibodies against transfused red blood cells (RBCs) can pose a serious health risk, especially in chronically transfused patients requiring life-long transfusion support; yet our understanding of what immune signals or cells dictate when someone will become alloimmunized is lacking. The relative role of dendritic cells, B cells and macrophages in the induction of RBC alloimmunization remain unclear. Given the now well established role of innate immune signals in regulating adaptive immunity, understanding if and how innate immunity is triggered during transfusion may allow development of therapies to prevent alloimmunization in chronically transfused subjects such as those with myelodysplasia or hemoglobinopathies. We have established a murine model system in which we can evaluate both the role of particular innate immune stimuli as well as particular cells of the immune system in regulating the allogeneic response to transfused RBCs. A particularly useful transgenic "HOD mouse" has been engineered, which encodes a triple fusion protein and provides a unique tool to directly assess both RBC-specific T and B cell responses. This RBC-specific antigen contains the model protein antigen hen egg lysozyme (HEL) fused to chicken ovalbumin (OVA) fused to the human Duffyb blood group antigen (HEL-OVA-Duffy) as an integral membrane protein under control of the beta globin promoter. Transfusion of genetically targeted mice lacking various innate immune cells or receptors allows us to screen for important immune pathways regulating the response to allogeneic RBCs. Using these models, we recently discovered that mice lacking the GEF (guanine nucleotide exchange factor) DOCK8 fail to develop alloimmunity to transfused RBCs. Dendritic cells in these knockout mice fail to migrate to T cells due to lack of coordinated actin rearrangement governed by this GEF. Both B cell and T cell activation in the spleen to the transgenic transfused RBCs is abrogated. Inclusion of OVA in the alloantigen of the HOD mice allows us to readily study naïve CD4+ T cell activation following transfusion by using the OTII T cell receptor (TCR) transgenic mice in which essentially all T cells express one antigen receptor specific for a peptide of OVA. By tracking rounds of cell division we found that adoptively transferred OTII undergo more than 5-8 rounds of division in the spleen three days following transfusion of HOD RBCs in WT recipients. In contrast, no OTII proliferation was observed in DOCK8-deficient mice following OTII adoptive transfer and HOD RBC transfusion, suggesting that T cells are failing to receive activation signals by splenic antigen presenting cells. Our preliminary data now suggest that DOCK8-deficient dendritic cells are able to process and present RBC-derived antigens, but do not migrate to T cell zones in the spleen to prime naïve RBC-specific T cells. The need for dendritic cell migration within the spleen in the induction of alloimmunity to transfused RBCs has not been addressed; these mice allow us for the first time to answer these fundamental immunologic questions during transfusion. Future work will aim to determine how dendritic cell movement within the spleen is regulated during transfusion and the specific role of splenic dendritic cell subsets in CD4+ T cell priming to allogeneic RBCs. Disclosures No relevant conflicts of interest to declare.

Mouse model for analysis of non-MHC genes that influence allogeneic response: recombinant congenic strains of OcB/Dem series that carry identical H2 locus

2006 ◽  
Vol 1 (1) ◽  
pp. 16-28 ◽  
Author(s):  
Helena Havelková ◽  
Vladimír Holáň ◽  
Igor Kárník ◽  
Marie Lipoldová
Keyword(s):  
Mouse Model ◽  
Clinical Manifestations ◽  
Cell Receptor ◽  
Primary Immune Response ◽  
Congenic Strains ◽  
Mhc Genes ◽  
Receptor Signal ◽  
Recombinant Congenic Strains ◽  
Highly Correlated ◽  
Allogeneic Response

AbstractAlloreactivity is the strongest known primary immune response. Its clinical manifestations are graft rejection, graft-versus-host disease and graft-versus-leukemia effect. The strongest stimulation by allogeneic cells is due to incompatibility at the major histocompatibility complex (MHC) genes. However, the non-MHC genes also participate in allogeneic response. Here we present a mouse model for study of the role of non-MHC genes in regulation of alloreactivity and show that they besides encoding antigens also regulate the responsiveness. Recombinant congenic strains (RCS) of O20/A (O20)-c-B10.O20/Dem (OcB/Dem) series have been derived from the parental strains O20 and B10.O20, which carry identical MHC haplotypes (H2pz) and therefore their differences in alloantigen response depend only on non-MHC genes. We have tested a MLR response by spleen cells of the strains O20, B10.O20, and 16 OcB/Dem strains through stimulation by cells from strains C57BL/10 (H2b), BALB/c (H2d), CBA (H2k), and DBA/1 (H2q) alloantigens. Proliferative response of O20, B10.O20 and OcB/Dem strains to these four alloantigens exhibited a similar but not completely identical pattern of reactivity. The responses to different alloantigens were highly correlated: C57BL/10-BALB/c r = 0.87, C57BL/10-CBA r = 0.84, C57BL/10-DBA/1 r = 0.83. Cluster analysis of the responses by O20, B10.O20, and OcB mice identified groups of strains with distinct patterns of response. This data shows that two main types of genes influence MLR: 1. structural genes for major and minor alloantigens and 2. genes regulating T-cell receptor signal transduction or mediating costimulatory signals by antigen-presenting cells.

scholarly journals Human γδ+ T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response

2001 ◽  
Vol 27 (6) ◽  
pp. 601-606 ◽  
Author(s):  
LS Lamb ◽  
P Musk ◽  
Z Ye ◽  
F van Rhee ◽  
SS Geier ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Allogeneic Response

scholarly journals Benefit of Belatacept in Cord Blood-Derived Regulatory T Cell-Mediated Suppression of Alloimmune Response

2021 ◽  
Vol 30 ◽  
pp. 096368972110465
Author(s):  
Xing He ◽  
Sang Li ◽  
Juan Zhang ◽  
Lu Cao ◽  
Cejun Yang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Tolerance Induction ◽  
Mitochondrial Metabolism ◽  
Functional Markers ◽  
Post Transplantation ◽  
Transplant Tolerance ◽  
The Stability ◽  
Allogeneic Response

The role of Regulatory T cells (Tregs) in tolerance induction post-transplantation is well-established, but Tregs adoptive transfer alone without combined immunosuppressants have failed so far in achieving clinical outcomes. Here we applied a set of well-designed criteria to test the influence of commonly used immunosuppressants (belatacept, tacrolimus, and mycophenolate) on cord blood-derived Tregs (CB-Tregs). Our study shows that while none of these immunosuppressants modulated the stability and expression of homing molecules by CB-Tregs, belatacept met all other selective criteria, shown by its ability to enhance CB-Tregs-mediated in vitro suppression of the allogeneic response without affecting their viability, proliferation, mitochondrial metabolism and expression of functional markers. In contrast, treatment with tacrolimus or mycophenolate led to reduced expression of functional molecule GITR in CB-Tregs, impaired their viability, proliferation and mitochondrial metabolism. These findings indicate that belatacept could be considered as a candidate in Tregs-based clinical immunomodulation regimens to induce transplant tolerance.

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