scholarly journals The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism

2021 ◽  
Vol 22 (20) ◽  
pp. 11104
Author(s):  
Dante De Paz ◽  
Ana Elena Aviña ◽  
Esteban Cardona ◽  
Chin-Ming Lee ◽  
Chia-Hsien Lin ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Oral Mucosa ◽  
Immunosuppressive Drugs ◽  
Mixed Chimerism ◽  
Allograft Survival ◽  
T Helper 1 ◽  
Significant Prolongation ◽  
Anti Inflammatory

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

scholarly journals MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jian Lu ◽  
Weiwei Wang ◽  
Peiyuan Li ◽  
Xiaodong Wang ◽  
Chao Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Rejection ◽  
Mouse Heart ◽  
Allograft Survival ◽  
Treg Function ◽  
Ifn Γ ◽  
Heart Transplant Rejection

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.

scholarly journals CD4+ CD25+ Regulatory T Cells Modulate the T-Cell and Antibody Responses in Helicobacter-Infected BALB/c Mice

2006 ◽  
Vol 74 (6) ◽  
pp. 3519-3529 ◽  
Author(s):  
Maria Kaparakis ◽  
Karen L. Laurie ◽  
Odilia Wijburg ◽  
John Pedersen ◽  
Martin Pearse ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Bacterial Colonization ◽  
Antibody Responses ◽  
T Helper 1 ◽  
Time Of Infection ◽  
Lymph Node Cells ◽  
Antibody Levels ◽  
And Control

ABSTRACT Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter-infected, normal mice depleted of CD4+ CD25+ T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4+ CD25+ T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25+ Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25+ Tregs was associated with increased Helicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25+ Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25+ Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25+ Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter-infected mice depleted of CD25+ Tregs but is induced in CD25+ Treg-depleted mice, which have a higher frequency of autoreactive T cells.

Mesenchymal stem cells induce the expansion of regulatory T cells in abortion-prone mice

Reproduction ◽  
2021 ◽  
Author(s):  
Amir Salek Farrokhi ◽  
Amir-Hassan Zarnani ◽  
Fatemeh Rezaei kahmini ◽  
Seyed Mohammad Moazzeni
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
De Novo ◽  
Abortion Rate ◽  
Cellular Mechanisms ◽  
Inguinal Lymph Nodes

Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph nodes, and Ho1, Foxp3, Pd1, and Ctla4 genes expression at the feto-maternal interface were then measured on day 13.5 of pregnancy using flow cytometry and quantitative RT- PCR, respectively. The abortion rate in MSCs-treated mice was significantly reduced and normalized to the level observed in normal pregnant animals. We demonstrated a significant induction of Tregs in inguinal lymph nodes but not in the spleen following MSCs administration. Administration of MSCs remarkably upregulated the expression of HO1, Foxp3, Pd1, and Ctla4 genes in both placenta and decidua. Here, we show that MSCs therapy could protect the fetus in the abortion-prone mice through Tregs expansion and up-regulation of Treg-related genes. These events could establish an immune-privileged microenvironment, which participates in regulation of detrimental maternal immune responses against the semi-allogeneic fetus.

scholarly journals Immune activation and regulatory T cells in Mycobacterium tuberculosis infected lymph nodes

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Karima Sahmoudi ◽  
Hassan Abbassi ◽  
Nada Bouklata ◽  
Mohamed Nouredine El Alami ◽  
Abderrahmane Sadak ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Immune Activation

scholarly journals Regulatory T cells with superior immunosuppressive capacity emigrate from the inflamed colon to draining lymph nodes

2017 ◽  
Vol 11 (2) ◽  
pp. 437-448 ◽  
Author(s):  
Y Nakanishi ◽  
R Ikebuchi ◽  
T Chtanova ◽  
Y Kusumoto ◽  
H Okuyama ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Draining Lymph Nodes
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