scholarly journals LYMPH NODE REGULATORY T-CELL IN Muc2-/- MICE WITH HELICOBACTER SPP.

2021 ◽  
Vol 23 (4) ◽  
pp. 629-634
Author(s):  
K. M. Achasova ◽  
O. V. Gvozdeva ◽  
E. N. Kozhevnikova ◽  
E. A. Litvinova
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Regulatory Function ◽  
Wild Type ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Vital Functions

The immune processes associated with the formation of resistance to pathogens in the intestine depend on the microbiome. The maintenance of homeostasis in the intestine is provided by regulatory T-cells. In inflammatory bowel disease (IBD), both a disturbance of the T-regulatory function and changes in microflora are observed. Aggravation of the disease is accompanied by various infections. However, pathobionts such as Helicobacter spp., can affect regulatory T-cells. One of the genetic models for studying IBD is Muc2 knockout mice. In these mice, as in humans with IBD, intestinal epithelial and immune cells closely interact with the microflora. It is believed that the immune cells of the lymph nodes Muc2-/- mice are sensitive to changes in the microflora formed in them. In this study, the effect of Helicobacter spp. on the number and percentage of different types of leukocytes and T regulatory cells in the mesenteric lymph nodes of Muc2-/- mice was studied. The number of CD45+CD19+, CD45+CD3+, CD45+CD3+CD4+, CD45+CD3+CD8+-cells in the mesenteric lymph nodes of Muc2-/- mice was significantly higher to compare with wild-type Muc2+/+ mice. However, the presence of infection in Muc2-/- mice canceled the increase in the number of CD45+CD19+, CD45+CD3+, CD45+CD3+CD4+, CD45+CD3+CD8+-cells. In wild-type Muc2+/+ mice, infection had no significant effect on cells in mesenteric lymph nodes. This change in the decrease in immune cells in the mesenteric lymph nodes under the Helicobacter spp. may be associated with the activation of regulatory T-cells. Indeed, it has been shown that the presence of a congenital Helicobacter spp. infection increased of the number of regulatory T-cells (CD45+CD4+CD25+FoxP3+) in the mesenteric lymph nodes. Well known that regulatory T-cells mediate anti-inflammatory responses in the gut. Thus, an increase in regulatory T-cells promotes a decrease in all types of immune cells in the mesenteric lymph nodes of Muc2-/- mice infected with Helicobacter spp. It could provide an improvement in the vital functions of these mice and possibly reduces inflammatory responses in the intestine. This may indicate that some congenital pathobionts activate of the regulatory mechanisms of immunity and, thereby, have a beneficial effect on the host. 

scholarly journals Expression of Regulatory T Cells in Jejunum, Colon, and Cervical and Mesenteric Lymph Nodes of Dogs Naturally Infected with Leishmania infantum

2014 ◽  
Vol 82 (9) ◽  
pp. 3704-3712 ◽  
Author(s):  
Maria M. Figueiredo ◽  
Beatriz Deoti ◽  
Izabela F. Amorim ◽  
Aldair J. W. Pinto ◽  
Andrea Moraes ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Leishmania Infantum ◽  
Parasite Load ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Mesenteric Lymph ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTUsing flow cytometry, we evaluated the frequencies of CD4+and CD8+T cells and Foxp3+regulatory T cells (Tregs) in mononuclear cells in the jejunum, colon, and cervical and mesenteric lymph nodes of dogs naturally infected withLeishmania infantumand in uninfected controls. All infected dogs showed chronic lymphadenitis and enteritis. Despite persistent parasite loads, no erosion or ulcers were evident in the epithelial mucosa. The colon harbored more parasites than the jejunum. Frequencies of total CD4+, total Foxp3, and CD4+Foxp3+cells were higher in the jejunum than in the colon. Despite negative enzyme-linked immunosorbent assay (ELISA) serum results for cytokines, levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α) were higher in the jejunum than in the colon for infected dogs. However, IL-4 levels were higher in the colon than in the jejunum for infected dogs. There was no observed correlation between clinical signs and histopathological changes or immunological and parasitological findings in the gastrointestinal tract (GIT) of canines with visceral leishmaniasis. However, distinct segments of the GIT presented different immunological and parasitological responses. The jejunum showed a lower parasite load, with increased frequencies and expression of CD4, Foxp3, and CD8 receptors and IL-10, TGF-β, IFN-γ, and TNF-α cytokines. The colon showed a higher parasite load, with increasing expression of IL-4.Leishmania infantuminfection increased expression of CD4, Foxp3, IL-10, TGF-β, IFN-γ, and TNF-α and reduced CD8 and IL-4 expression in both the jejunum and the colon.

Abrogation of Donor T Cell IL-21 Signaling Leads to Tissue-Specific Modulation of Immunity and Separation of Gvhd From GVL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 729-729
Author(s):  
Alan M. Hanash ◽  
Lucy W. Kappel ◽  
Nury L. Yim ◽  
Rebecca A. Nejat ◽  
Gabrielle L. Goldberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Wild Type ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Donor T Cells

Abstract Abstract 729 Allogeneic hematopoietic transplantation is frequently the only curative therapy available to patients with hematopoietic malignancies, however transplant success continues to be limited by complications including graft vs. host disease (GVHD) and disease relapse. Separation of GVHD from graft vs. leukemia/lymphoma (GVL) responses continues to be a major goal of experimental and clinical transplantation, and better understanding of T cell immunobiology may lead to novel strategies to accomplish this goal. Interleukin 21 (IL-21) is a pro-inflammatory cytokine produced by Th17 helper T cells, and abrogation of IL-21 signaling has recently been demonstrated to reduce GVHD while retaining GVL. However, the mechanisms by which IL-21 may lead to a separation of GVHD and GVL are incompletely understood. In order to characterize the effect of IL-21 on GVH and GVL T cell responses, we compared wild type and IL-21 receptor knockout (IL-21R KO) donor T cells in a C57BL/6 into BALB/c murine MHC-mismatched bone marrow transplant (BMT) model. Lethally irradiated BMT recipients of IL-21R KO T cells demonstrated decreased GVHD-related morbidity (p<.05) and mortality (p<.01), and decreased histopathologic evidence of GVHD within the small intestine (p<.05). While this reduction in IL-21R KO T cell-mediated GVHD was associated with increased donor regulatory T cells two to three weeks post-BMT (p<.001), IL-21 signaling in both donor CD4 and donor CD8 T cells was found to contribute to GVHD mortality (p<.01 for CD4, p<.05 for CD8). Analysis of IL-21R expression by wild type T cells demonstrated receptor upregulation upon polyclonal activation in vitro and upon alloactivation in vivo (p<.01). However, this IL-21R upregulation was not required for in vivo alloactivation, as IL-21R KO and wild type donor T cells demonstrated equivalently greater proliferation in allogeneic vs. syngeneic recipients (p<.001), equivalent upregulation of CD25 (p<.001), and equivalent downregulation of CD62L (p<.01 for CD8 T cells). Despite this equivalent alloactivation, IL-21R KO T cells demonstrated decreased infiltration within the small intestine (p<.05), decreased infiltration in mesenteric lymph nodes (p<.05 for CD8 T cells, p<.001 for CD4 T cells), and decreased inflammatory cytokine-producing CD4 T cells within mesenteric lymph nodes (p<.01 for IFN-g, p<.001 for TNF-a, Figure 1A). Consistent with this, transplanted IL-21R KO donor T cells demonstrated decreased expression of a4b7 integrin (LPAM, p<.05), a molecule known to be involved in homing of GVHD-mediating donor T cells to the gut. However, in contrast to the reduced inflammatory cytokine-producing CD4 T cells observed in mesenteric lymph nodes, IL-21R KO helper T cell cytokine production was maintained in spleen (Figure 1B) and peripheral lymph nodes, and IL-21R KO T cells were able to protect recipient mice from lethality due to A20 lymphoma (p<.001). In summary, abrogation of IL-21 signaling in donor T cells leads to tissue-specific modulation of immunity, such that gastrointestinal GVHD is reduced, but peripheral T cell function and GVL capacity are retained. Targeting IL-21 for therapeutic intervention is an exciting strategy to separate GVHD from GVL, and this novel approach should be considered for clinical investigation to improve transplant outcomes and prevent malignant relapse. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The influence of Th1/Th2 and CD4 + regulatory t cells of mesenteric lymph nodes on systemic lipopolysaccharide

2014 ◽  
Vol 2 ◽  
pp. 125-129 ◽  
Author(s):  
Wenli Yu ◽  
Hongyin Du ◽  
Qiang Fu ◽  
Naiqiang Cui ◽  
Chao Du
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

In Vivo Trafficking of CD4+CD25+ Regulatory T-Cells in Allogeneic Recipients Using Bioluminescence Imaging.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 302-302
Author(s):  
Vu H. Nguyen ◽  
Courtney Wieland ◽  
Christopher Contag ◽  
Robert S. Negrin
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Immune Cells ◽  
Signal Intensity ◽  
Bioluminescence Imaging ◽  
Control Group ◽  
Wild Type

Abstract CD4+CD25+ regulatory T-cells (Treg) have the potential to suppress aberrant immune responses and to regulate peripheral T cell homeostasis. In a murine allogeneic bone marrow transplantation (BMT) model, our laboratory has previously shown that Treg suppress graft-versus-host-disease (GVHD) without abrogating the beneficial graft-versus-tumor immunological effect. However, the mechanisms of immuno-regulation, in particular, the allorecognition properties of Treg, their effects on and interaction with other immune cells, and the sites of suppressive activity, remain unclear. In the current study, we investigate the in vivo trafficking of Treg to better understand how localization may affect their regulatory function. Interpretation of previous studies of Treg localization has been limited by several factors: the need to sacrifice mice does not permit tracking the same set of cells over time; data collected at several arbitrary times on selected tissues do not permit accurate determination of primary and secondary sites of migration, activation, proliferation, and suppression; and CD25 expression on activated CD4+CD25- T cells are difficult to distinguish from Treg. We have developed and characterized a transgenic mouse which constitutively expresses the luciferase gene in all hematologic cells. Treg (1x106 cells) from the spleen and lymph nodes of luc+ transgenic FVB/N (H-2q) mice were co-transplanted into lethally-irradiated (800cGy) Balb/c (H-2d) host along with 5x106 wild-type FVB/N T-cell depleted bone marrow (TCD-BM) cells and 2x106 whole splenocytes, the latter containing approximately 30% T cells (Tconv) which induce GVHD. Upon exposure to the substrate luciferin, the luciferase-expressing Treg emit light which can penetrate through living tissues and is captured by sensitive CCD camera detectors. Bioluminescence imaging (BLI) was performed at various time points established previously by our studies of BLI in GVHD. Within the first 48 hours, Treg localized to the cervical lymph nodes (LN) and the spleen. By day 3, signal is detected in other LN (axillary, mesenteric, inguinal) as well as Peyer’s patches and liver. Signal intensity, measured by photons/second/mouse, significantly increased and peaked on day 4, consistent with the migration and proliferation of Treg to and at these secondary lymphoid organs, respectively. Skin infiltration of Treg is noted on day 6, congruent with a decreased intensity in the spleen, liver, and lymph nodes. A similar pattern of early migration and proliferation of effector immune cells is noted in the GVHD control group, which is transplanted with wild-type FVB/N TCD-BM and luc+ FVB/N whole splenocytes. However, with the GVHD group, the signal intensity continues to increase at all sites. Continued BLI of the Treg group up to day 45 demonstrates persistent strong signal in lymphoid organs and skin sites. Clinically, the Treg group has no significant evidence of GVHD. Chimerism studies on day 45 show complete donor origin, however, lymphoid reconstitution of CD4+ and CD8+ T cells is delayed in the GVHD control group and enhanced in the recipients transplanted with Treg. The above results indicate that in vivo, Treg proliferate and survive long-term. In addition, they co-localize with effector immune cells to secondary lymphoid tissues to positively impact clinical outcomes and lymphoid reconstitution following major-MHC mismatched BMT.

Sign in / Sign up

Export Citation Format

Share Document