scholarly journals Immuno-modulatory Role of Indoleamine 2, 3-Dioxygenase in Allogeneic Islet and Skin Transplantation

2013 ◽  
pp. 1-17 ◽  
Author(s):  
Pavandeep Gill ◽  
Reza Jalili ◽  
Aziz Ghahary
Keyword(s):  
Skin Transplantation ◽  
Indoleamine 2

scholarly journals The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity

Vaccines ◽  
2015 ◽  
Vol 3 (3) ◽  
pp. 703-729 ◽  
Author(s):  
Jacques Mbongue ◽  
Dequina Nicholas ◽  
Timothy Torrez ◽  
Nan-Sun Kim ◽  
Anthony Firek ◽  
...  
Keyword(s):  
Immune Suppression ◽  
Indoleamine 2

A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 688-688
Author(s):  
Isao Tawara ◽  
Tomomi Toubai ◽  
Chelsea Malter ◽  
Yaping Sun ◽  
Evelyn Nieves ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Indoleamine 2 ◽  
Effector Phase ◽  
Antigen Presenting

Abstract Abstract 688 Several lines of evidence show that donor derived mature CD4+CD25+Foxp3+ regulatory T cells (Tregs) suppress experimental GVHD. The mechanism of GVHD suppression by donor Tregs is, however, not well understood. Recent observations have brought in a renewed focus on the role of professional antigen presenting cells (APCs) in the induction and maintenance of GVHD by alloreactive T cell effectors (Teffs). But the role of APCs in modulating the responses of Tregs after allogeneic BMT is not known. We first tested the requirement of host APCs in Treg mediated regulation of GVHD. We utilized a clinically relevant CD8+ T cell dependent MHC matched but miHA disparate C3H.SW (H-2b) → wild type (wt) or Class II deficient Abb (II-/-) B6 (H-2b) model of GVHD because host APCs and target tissues from the Abb animals do not express class II and as such donor CD4+CD25+ Tregs will not directly interact with the host tissues while alloreactive CD8+ T cells could still respond to miHA allo-antigens presented by the intact class I on host APCs. The recipient Abb (II-/-) and wt B6 animals were lethally irradiated and transplanted with 2 × 105 CD8+ T cells along with or without CD4+CD25+ Tregs at 1:2 ratio from either syngeneic B6 or allogeneic C3H.SW animals. The wt recipients that received Tregs showed significantly better survival compared with the wt animals that did not receive any Tregs (P< 0.01) while the class II-/- animals showed similar GVHD mortality regardless of Treg infusion (P>0.8). To confirm whether the lack of Treg mediated protection was only due to the absence of interaction with host type APCs and also to exclude the possibility of development of Tregs from the infused BM we thymectomized wt B6 animals and then generated [B6 B6] controls and the [Abb B6] chimeras. These chimeric animals were used as recipients in a second BMT and transplanted with CD8+ Teffs and Tregs from allogeneic C3H.SW mice. Tregs reduced GVHD mortality in the [B6 B6] (P<0.01) but not in the [Abb B6] animals (P>0.7). We next evaluated whether host APC expression of allo-antigens alone was sufficient for Treg mediated GVHD protection in the absence of class II expression on target tissues by generating [B6 B6] and [B6 Abb] chimeras and found that Tregs demonstrated equivalent GVHD protection even when the class II allo-antigens were expressed only on the host APCs. Mechanistic studies demonstrated that Tregs significantly inhibited the expansion of CD8+ Teffs on days +10 and 17 after BMT in the spleens of the WT recipients (P<0.05) but not in the class II-/- animals. However, infused Tregs demonstrated reduced expansion in the class II-/- animals only early after BMT (on day +10) but was equivalent at later time-point (days 17 and 29) to the WT recipients. We further determined the mechanisms by which host APCs might contribute to Treg mediated protection. To this end we used IL-10-/-, indoleamine 2, 3 dioxygenase (IDO)-/- deficient animals and generated [IL-10-/- B6] and [IDO-/- B6] animals as recipients. Tregs mitigated GVHD mortality regardless of the ability of the host APCs to express IL-10 or IDO. We next determined whether Tregs suppressed Teffs in their activation phase at the level of their interaction with host APCs or in the effector phase. C3H.SW CD8+ T cells were primed (both in vivo and ex vivo with B6 allo-antigens) and then infused into the [β2mg-/- B6] animals such that pre-activated CD8 Teffs would still be able to initiate GVHD without the need for host APCs for their activation. Infusion of donor Tregs into [β2mg-/- B6] animals that were transplanted with the pre-activated Teffs mitigated GVHD severity demonstrating that Tregs, once activated by host APCs, were capable of suppressing Teff cells in their effector phase. Collectively our data show (a) host APCs are critical (b) expression of allo-antigens on host target tissues is not obligatory (c) host derived IL-10 and IDO are not critical for Treg mediated GVHD protection and (d) Tregs can mitigate GVHD by suppressing alloreactive Teffs in the effector phase even after they have been activated. Disclosures: No relevant conflicts of interest to declare.

Essential Role of Indoleamine 2, 3‐dioxygenase 1 ( IDO1 ) in Metabolic Programming of Innate Immune Responses in Aged Lung during Influenza

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Heather W. Stout-Delgado ◽  
Rebecca Harris ◽  
Jianjun Yang ◽  
Kyung Sook Hong ◽  
Soo Jung Cho
Keyword(s):  
Immune Responses ◽  
Essential Role ◽  
Metabolic Programming ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Indoleamine 2

Critical Role of IFNg in Allograft Tolerance Mediated by Foxp3+CD4+CD25+ Regulatory T Cells and the Production of Indoleamine 2, 3-dioxygenase by Graft Endothelial Cells

2007 ◽  
Vol 123 ◽  
pp. S130-S131
Author(s):  
Pamela Thebault ◽  
Michele Heslan ◽  
Thomas Condamine ◽  
Abdelhadi Saoudi ◽  
Marcello Hill ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Regulatory T Cells ◽  
Critical Role ◽  
Indoleamine 2

scholarly journals Skin transplantation in mice as an animal model for functional analysis of T regulatory cells.

2018 ◽  
Vol 74 (1) ◽  
pp. 6034-2018
Author(s):  
ANNA ŻYŁKO ◽  
ANNA WARDOWSKA ◽  
PIOTR TRZONKOWSKI
Keyword(s):  
Multiple Sclerosis ◽  
Allograft Rejection ◽  
T Regulatory Cells ◽  
Tolerance Induction ◽  
Skin Grafting ◽  
Immunological Tolerance ◽  
Skin Transplantation ◽  
Regulatory Cells ◽  
Immune Tolerance Induction

The role of T regulatory cells (Tregs) in transplantology has been widely studied over the years. The mouse model of skin transplantation is used as a quick and easy way to monitor the immune response of Tregs, vital for creation and maintenance of homeostasis and immunological tolerance. This model is extremely useful in the assessment of allograft rejection and immune tolerance induction dependent on Tregs. The procedure of skin transplantation is widely used not only in transplantology, but also in studies on the effectiveness of various immunosuppressive compounds and studies on autoimmune diseases, including diabetes, multiple sclerosis and albinism. The improved protocol of mouse tail skin grafting is easy to master, and its wide application gives many opportunities for new solutions in biomedical research..

The Role of Adiponectin in an Experimental Model of Allogeneic Skin Transplantation.

2014 ◽  
Vol 98 ◽  
pp. 330
Author(s):  
M. da Silva ◽  
M. Amano ◽  
W. Festuccia ◽  
M. Hiyane ◽  
A. Silva e Filho ◽  
...  
Keyword(s):  
Experimental Model ◽  
Skin Transplantation

scholarly journals The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression

2011 ◽  
Vol 165 (2) ◽  
pp. 251-263 ◽  
Author(s):  
J. de Souza Sales ◽  
F. A. Lara ◽  
T. P. Amadeu ◽  
T. de Oliveira Fulco ◽  
J. A. da Costa Nery ◽  
...  
Keyword(s):  
Lepromatous Leprosy ◽  
Indoleamine 2

scholarly journals Tryptophan: From Diet to Cardiovascular Diseases

2021 ◽  
Vol 22 (18) ◽  
pp. 9904
Author(s):  
Nada Joe Melhem ◽  
Soraya Taleb
Keyword(s):  
Immune Responses ◽  
Acid Metabolism ◽  
Inflammatory Responses ◽  
Common Mechanism ◽  
Specific Cell ◽  
Indoleamine 2 ◽  
Adaptive Immune ◽  
Causes Of Mortality ◽  
One Step

Cardiovascular disease (CVD) is one of the major causes of mortality worldwide. Inflammation is the underlying common mechanism involved in CVD. It has been recently related to amino acid metabolism, which acts as a critical regulator of innate and adaptive immune responses. Among different metabolites that have emerged as important regulators of immune and inflammatory responses, tryptophan (Trp) metabolites have been shown to play a pivotal role in CVD. Here, we provide an overview of the fundamental aspects of Trp metabolism and the interplay between the dysregulation of the main actors involved in Trp metabolism such as indoleamine 2, 3-dioxygenase 1 (IDO) and CVD, including atherosclerosis and myocardial infarction. IDO has a prominent and complex role. Its activity, impacting on several biological pathways, complicates our understanding of its function, particularly in CVD, where it is still under debate. The discrepancy of the observed IDO effects could be potentially explained by its specific cell and tissue contribution, encouraging further investigations regarding the role of this enzyme. Thus, improving our understanding of the function of Trp as well as its derived metabolites will help to move one step closer towards tailored therapies aiming to treat CVD.

IFNγ Licensed Human Bone Marrow Derived Mesenchymal Stromal Cells Inhibit T Cell Cytokine Production by a Mechanism Independent of Indoleamine 2 3-Dioxygenase (IDO) Activity

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1255-1255
Author(s):  
Raghavan Chinnadurai ◽  
Ian Copland ◽  
Seema Patel ◽  
Jacques Galipeau
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Intracellular Cytokine Staining ◽  
Cytokine Secretion ◽  
T Cell Proliferation ◽  
Indoleamine 2 ◽  
T Cell Function ◽  
Inhibitory Potential

Abstract Abstract 1255 Human Bone marrow derived Mesenchymal Stromal Cells (MSCs) inhibit activation-mediated T cell proliferation. This functional interaction serves nearly universally as a surrogate assay for immune suppressive activity and potency of MSCs in vitro. However the role of MSCs in inhibiting T cell function, cytokine production in particular, has not been investigated thoroughly. In the present study we have compared resting MSCs with IFNγ licensed MSCs for their ability to inhibit activated T cell function such as cytokine secretion and degranulation through intracellular cytokine staining assays. PBMCs cocultured with resting or inflammatory cytokine licensed MSCs were stimulated with the super antigen Stephylococcal Enterotoxin B (SEB) for 12–14hours in the presence of Brefeldin A. Intracellular cytokine staining was performed on the T cells to detect the Interferon gamma (IFNγ), Tumor Necrosis Alpha (TNFα) and Interleukin-2 (IL-2). Our results demonstrate that resting MSCs do not inhibit T cell cytokine secreting function. However, IFNγ and IFNγ plus TNFα licensed MSCs dose dependently inhibit IFNγ secretion by T cells. Our results also show that IFNγ and IFNγ plusTNFα licensed MSCs not only inhibit cytokine secretion but also inhibit dregranulation of activated T cells. Boolean gating analysis demonstrates that IFNγ and IFNγ plusTNFα licensed MSCs inhibit triple cytokine producing highly inflammatory IFNγ +TNFα +IL2+T cells. Phenotypic analysis of MSCs demonstrates that IFNγ licensing upregulate indoleamine 2 3-dioxygenase (IDO) and B7-H1. Blocking of IDO activity with 1-Methyl D,L Tryptophan (1MT) will abolish MSC-mediated blockade of T cell proliferation. However, 1MT does not reverse the MSC blockade of T cell cytokine secretion. Phenotypical analysis of T cells demonstrate that PD1+ cells are inhibited while PD1- cells are not inhibited suggesting the role of B7-H1 and PD-1 inhibitory pathway is involved in the inhibitory potential of IFNγ licensed MSCs. Interestingly, the inhibitory potential of IFNγ licensed MSCs has been observed only with the SEB stimulation but not with anti-CD3, CD28 stimulation. This suggests that MHC-TCR interaction is necessary for the inhibitory effect of IFNγ licensed MSCs. Our results demonstrate the superiority of IFNγ licensed MSCs in inhibiting multiple cytokine producing T cell function independent of IDO activity. Our results also provide the rationale for use of IFNγ licensed MSCs in autologous immunosuppressive cell therapy. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document