scholarly journals Role of DC and chemokines for the induction of gut-homing CD4+CD25+ regulatory T cells in Peyer's patches

2003 ◽  
Vol 26 (4) ◽  
pp. 204-204
Author(s):  
Yoshinori KOMAGATA ◽  
Katsuya NAGATANI ◽  
Kazuhiko YAMAMOTO
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches

Antigen-specific regulatory T cells are detected in Peyer's patches after the interaction between T cells and dendritic cells loaded with orally administered antigen

Immunobiology ◽  
2011 ◽  
Vol 216 (3) ◽  
pp. 416-422 ◽  
Author(s):  
Katsuya Nagatani ◽  
Yoshinori Komagata ◽  
Kurumi Asako ◽  
Maki Takayama ◽  
Kazuhiko Yamamoto
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches

scholarly journals Parasite Proximity Drives the Expansion of Regulatory T Cells in Peyer's Patches following Intestinal Helminth Infection

2015 ◽  
Vol 83 (9) ◽  
pp. 3657-3665 ◽  
Author(s):  
Ilaria Mosconi ◽  
Lalit Kumar Dubey ◽  
Beatrice Volpe ◽  
Julia Esser-von Bieren ◽  
Mario M. Zaiss ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cytokine Production ◽  
Helminth Infection ◽  
Peyer's Patches ◽  
Intestinal Helminth ◽  
Peyer’S Patches ◽  
Intestinal Helminths ◽  
Content Type

Helminth infections are typically chronic in nature; however, the exact molecular mechanisms by which these parasites promote or thwart host immunity remain unclear. Worm expulsion requires the differentiation of CD4+T cells into Th2 cells, while regulatory T cells (Tregs) act to dampen the extent of the Th2 response. Priming of T cells requires drainage or capture of antigens within lymphoid tissues, and in the case of intestinal helminths, such sites include the mucosa-associated Peyer's patches (PPs) and the draining mesenteric lymph nodes (MLN). To gain insight into when and where the activation of the adaptive T cell response takes place following intestinal helminth infection, we analyzed Th2 and Treg responses in the PPs and MLN following infection with the murine intestinal helminthHeligmosomoides polygyrusbakeri. Protective Th2 responses were observed to be largely restricted to the MLN, while a greater expansion of Tregs occurred within the PPs. Interestingly, those PPs that formed a contact with the parasite showed the greatest degree of Treg expansion and no evidence of type 2 cytokine production, indicating that the parasite may secrete products that act in a local manner to selectively promote Treg expansion. This view was supported by the finding thatH. polygyrusbakerilarvae could promote Treg proliferationin vitro. Taken together, these data indicate that different degrees of Treg expansion and type 2 cytokine production occur within the PPs and MLN following infection with the intestinal helminthH. polygyrusbakeriand indicate that these organs exhibit differential responses following infection with intestinal helminths.

IL-18 and Antigen-Specific CD4+Regulatory T Cells in Peyer's Patches

2004 ◽  
Vol 1029 (1) ◽  
pp. 413-415 ◽  
Author(s):  
NORIKO M. TSUJI ◽  
BERNADETA NOWAK
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches

scholarly journals Manipulation of Induced Foxp3+ Regulatory T Cells for Prevention of Mouse Acute Graft-Versus-Host Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5605-5605
Author(s):  
Tzeon-Jye Chiou ◽  
Yi-Chun Ke ◽  
Chun-Tse Kuo ◽  
Hsiu-Yuan Huang ◽  
Shao-Chun Lu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Survival Rate ◽  
Regulatory T Cells ◽  
Bone Marrow Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Naive T Cells ◽  
Naïve T Cells

Background Foxp3+ regulatory T cells (Tregs) comprise of natural (n) and induced (i) Treg subsets play an important role in immune system. Currently, isolation of nTregs and in vitro-expanded nTregs was shown to be an effective therapy to GVHD patients. However, shortage of nTregs in peripheral blood and time consumption of expansion in vitro may eventually limit the clinical application. Conversely, iTregs can be generated in vitro from naïve T cells and to a large number of iTregs in short time. As we known, regulatory T cells would decay after a period of time, in vivo or in vitro. Keeping a certain number of iTregs during the GVHD treatment is necessary, it should be the best to provide iTregs to the patient more than single usage. Aim Manipulated supplements of TGF-β1-induced Foxp3+ regulatory T cells should be a good way for prevention from acute graft-versus-host disease within a short time. Investigation was performed via animal model. Methods Splenocytes from C57BL/6 mice were used as a source of naïve T cells by a CD4+ naïve T cell isolation Kit. To induce Foxp3+ regulatory T cells (iTregs), the CD4+ naïve T cells were incubated with anti-CD3/CD28 coated 24-well plate in the presence of IL-2 (20U/ml) and TGF-b1 (50ng/ml) for 3 days. Foxp3+iTregs were harvested and identified as the expressions of CD4+/CD25+/FoxP3+/CD127- via flow cytometry (Fig.1). In this experiment, recipients (BALB/c) were irradiated with 800cGy and then infused with donor (C57BL/6) bone marrow cells with (TCD-BM+CD4T) or without donor T cells (TCD-BM) by intravenous injection. TCD-BM+CD4T cells mice would appear aGVHD phenotype. 8x106 Foxp3+ iTregs were injected into the TCD-BM with donor T cell mouse one or twice (TCD-BM+CD4 T +iTreg) for immunosuppression assay as shown in Fig.2. Mouse GVHD phenotype, body weights and survival rates were investigated lasting for over 90 days. Tissue sections were stained with haematoxylin-eosin. Results According to our preliminary data, it indicated the injection of iTregs in the prevention of aGVHD should be feasible (Fig.3). Consequently, we have tried to investigate preventative efficiency of repeated iTregs supplements in TCD-BM mice. First of all, we compared the single-dose of iTregs with the repetition-dose of iTregs in aGVHD prevention. The data showed in Fig.4. The data showed that the survival rate was 73.3% in repeated treatment in mice, however, the survival rate was only 45.8% in single-dose of iTregs mice within 24 days. As the TCD-BM survival rate was 76.1%. It indicated that the repetition-dose of iTregs would prevent the occurrence of aGVHD, and the survival rate was similar as the bone marrow transplantation mice. The BM-CD4T mice with aGVHD phenotype could survive no more than 10 days. Furthermore, we investigated the survival time of the continual iTreg supplements mice. The data showed in Fig.5. After 90 days later, the body weight of iTregs treated mice could maintain the recovery efficiency to 83.8±2.1% and the survival rate to 78%, comparing with the TCD-BM mice was 88.8±0.6% and 73%. All of these mice could keep alive more than 90 days. Using histographic staining, we confirmed the aGVHD prevention with repeated supplement of Foxp3+iTregs to the CD4T mice (Fig.6). The mice, administration of CD4T cells with bone marrow cells, failed to survival for the serious damage of intestine villi (Fig.6A) and Peyer's patches (Fig.6B). In contrast, CD4T mice with Foxp3+-iTregs (iTregs) could survival more than 90 days and intestine villi were recovered after 90 days (Fig.6A). Peyer's patches are an important gut associated lymphoid tissue in small intestine and play a crucial role in immune response. Therefore, we have investigated the changes of Peyer's patches (Fig.6B). As the recovery of mice with iTregs for twice, the Peyer's patches reappeared after 90 days later. It indicated that keeping more iTregs in vivo could more efficient on prevention of aGVHD. It indicated that more alive iTregs to prevent GVHD occurrence more efficient and may provide the information pre-clinically. Conclusion We showed that repetition supplement of iTreg cells to TCD-BM+CD4T-treated mice, could maintain the mice in high survival rate. Therefore, we may provide more of the functional iTregs to GVHD patients, continuously. It's a good way to prevent the occurrence of GVHD. The result should develop a novel-cell based approach for potentially reducing the risk of acute GVHD clinically. Disclosures No relevant conflicts of interest to declare.

scholarly journals IL-4-Producing Vγ1+/Vδ6+ γδ T Cells Sustain Germinal Center Reactions in Peyer’s Patches of Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Leon Ullrich ◽  
Yvonne Lueder ◽  
Anna-Lena Juergens ◽  
Anneke Wilharm ◽  
Joana Barros-Martins ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Γδ T Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Γδ T Cell ◽  
First Line ◽  
Gut Homeostasis ◽  
Stimulation Of

The mucosal immune system is the first line of defense against pathogens. Germinal centers (GCs) in the Peyer’s patches (PPs) of the small intestine are constantly generated through stimulation of the microbiota. In this study, we investigated the role of γδ T cells in the GC reactions in PPs. Most γδ T cells in PPs localized in the GCs and expressed a TCR composed of Vγ1 and Vδ6 chains. By using mice with partial and total γδ T cell deficiencies, we found that Vγ1+/Vδ6+ T cells can produce high amounts of IL-4, which drives the proliferation of GC B cells as well as the switch of GC B cells towards IgA. Therefore, we conclude that γδ T cells play a role in sustaining gut homeostasis and symbiosis via supporting the GC reactions in PPs.

scholarly journals Astragaluspolysaccharide attenuates rat experimental colitis by inducing regulatory T cells in intestinal Peyer’s patches

2016 ◽  
Vol 22 (11) ◽  
pp. 3175 ◽  
Author(s):  
Hai-Mei Zhao ◽  
Yan Wang ◽  
Xiao-Ying Huang ◽  
Min-Fang Huang ◽  
Rong Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Colitis ◽  
Peyer's Patches ◽  
Peyer’S Patches

scholarly journals The Rap1-RIAM Pathway Regulates the Expression of Integrins αEβ7(CD103) and α4β7, Which Guide T Cell Homing to Intestinal Compartments

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 864-864
Author(s):  
Yavuz-Furkan Yazicioglu ◽  
Halil-Ibrahim Aksoylar ◽  
Rinku Pal ◽  
Nikolaos Patsoukis ◽  
Vassiliki A Boussiotis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adhesion Molecule ◽  
Lymphoid Organs ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
C Terminus ◽  
T Cell Homing ◽  
Secondary Lymphoid Organs

Abstract Integrin-mediated adhesion of lymphocytes to antigen presenting cells (APCs) links innate and adaptive immunity and is mandatory for the initiation of T cell immune responses. Control of lymphocyte adhesion to antigen-presenting cells (APC) is accomplished through the regulation of the principle adhesion molecule on the lymphocyte surface, lymphocyte functional antigen 1 (LFA-1), which binds to intercellular adhesion molecule 1 (ICAM-1) on the surface of APCs. Integrins also play crucial roles in cell migration to different immunological compartments such as the tumor microenvironment but also to targets of tissue and organ damage in autoimmune diseases and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. For these reasons, understanding the mechanisms implicated in LFA-1 activation and their functional implications is a subject of intense investigation. To mediate its adhesive function, LFA-1 must be activated via a process referred to as inside-out signaling, which results in conformation changes of the receptor that extends the ectodomains of the α and β chains leading to a high affinity state. Among the few signaling molecules that have been implicated in this process in hematopoietic cells are the small GTPase Rap1 and its downstream effector RIAM. RIAM is a multidomain protein that includes a talin binding region, two coiled-coiled regions, a small N-terminus proline-rich region, sequential Ras association (RA) and pleckstrin homology (PH) domains, and a large C-terminus proline-rich region, via which interacts with Ena/VASP family proteins and profilin and is recruited to the sites of actin turnover. Through its C-terminus RIAM also interacts with the SH3-domain of PLC-γ1.The RA and PH domains of RIAM function as an integral unit and as a proximity detector since both are required for translocation of RIAM to the plasma membrane. The RA domain of RIAM has specificity for Rap1-GTP whereas the PH domain binds to the PLC-γ1 substrate PI(4,5)P2. Upon interaction with Rap1-GTP, RIAM recruits talin to the LFA-1 β chain leading to its conformational change to the high-affinity state. Previously, we determined that Rap1-GTP induces expression of CD103 (integrin αE),which pairs with integrin beta 7 to form the complete heterodimer, integrin αEβ7. The chief ligand for αEβ7is E-cadherin, an adhesion molecule found on epithelial cells, important for T cell homing to intestinal sites. Moreover, expression of αEβ7(CD103) in T cells confers immunosuppressive and regulatory activity even in the absence of Foxp3. In the present study, we sought to investigate the role of Rap1-RIAM axis in the expression of integrins αEβ7(CD103) and α4β7, both responsible for T cell migration and homing to intestinal compartments, including Peyer's Patches, lamina propria and intestinal epithelium. We generated transgenic mice expressing constitutively active Rap1-GTP in T cells (Rap1-Tg) and mice with T cell-specific deletion of RIAM (RIAMf/fCD4cre). Rap1-Tg mice exhibited an increase of Teff-memory cell fractions, enhanced Treg cell differentiation and elevated expression of αEβ7(CD103), but significant reduction of total T cells in secondary lymphoid organs including Peyer's Patches, spleen and peripheric lymph nodes. These effects of Rap1-GTP were mediated by RIAM because these findings were reversed when RIAM was deleted in Rap1-Tg/RIAMf/fCD4cre mice. Consistent with a mandatory role of RIAM in these outcomes, RIAMf/fCD4cre mice displayed defective αEβ7(CD103) expression, particularly in the CD8+ T cell compartment, which inversely correlated with the expression of α4β7 resulting in > 2-fold increase of the CD8+ α4β7+ T cell fraction in secondary lymphoid organs. Rap1-Tg mice also exhibited enhanced Teff-memory, Th17 and T follicular helper (Tfh) cell differentiation in secondary lymphoid organs including Peyer's Patches, under steady-state conditions. In contrast to Treg differentiation, RIAM deletion in Rap1-Tg mice did not reduce Th17 and Tfh cells suggesting that RIAM plays a role in fate commitment processes of selective T helper cell subsets. Because αEβ7(CD103) and α4β7 guide T lymphocyte homing in the gut whereas the plasticity and reciprocal regulation of the Th17/Treg axis within gut-associated lymphoid tissues guard intestinal inflammation, our results suggest a selective role of the Rap1-RIAM pathway in gut-related immune pathologies. Disclosures No relevant conflicts of interest to declare.

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