scholarly journals Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain

2021 ◽  
Vol 12 ◽  
Author(s):  
Inés Ruedas-Torres ◽  
Jaime Gómez-Laguna ◽  
José María Sánchez-Carvajal ◽  
Fernanda Larenas-Muñoz ◽  
Inmaculada Barranco ◽  
...  
Keyword(s):  
T Cells ◽  
Post Infection ◽  
Fas Ligand ◽  
Respiratory Syndrome Virus ◽  
Γδt Cells ◽  
Tracheobronchial Lymph Node ◽  
Target Organs ◽  
Effector Cytokines ◽  
Biological Functionality ◽  
Virulence Target

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-γ in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and γδT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies.

scholarly journals Characterization of γδT Cells in Lung of Plasmodium yoelii-infected C57BL/6 Mice

2020 ◽  
Author(s):  
Haixia Wei ◽  
Chenxi Jin ◽  
Anping Peng ◽  
Hongyan Xie ◽  
Shihao Xie ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Post Infection ◽  
Absolute Number ◽  
Plasmodium Yoelii ◽  
Pathological Changes ◽  
Γδt Cells ◽  
Ifn Γ ◽  
And Function

Abstract BackgroundMalaria has high morbidity and mortality rates in most parts of tropical and subtropical countries. The lung not only works as a respiratory organ but also as an immune organ. γδT cells have multiple functions, producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of the mice infected by malaria. MethodsFlow cytometry (FCM) was used to evaluate the changes of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs.ResultsThe percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.05). The expressions of CD80, CD11b, and PD-1 in the γδT cells increased post-infection (p < 0.05), while the expressions of CD34, CD62L, and CD127 decreased (p < 0.05). γδT cells expressed more IL-4, IL-5, IL-6, IL-21, IL-1α, and IL-17 (p < 0.05), but less IFN-γ (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3+ cells, absolute numbers of CD3+ cells, CD3+ CD4+ cells, CD3+ CD8+ cells decreased in γδT KO infected mice (p < 0.05). γδT KO did not make a significant difference in the surface molecular expression of T cells (p > 0.05). While, the percentage of IFN-γ-expressing CD3+ and CD3+ CD8+ cells increased in γδT KO infected mice (p < 0.05). The absolute number of B cells was not affected by γδT KO. The B cells from infected γδT KO mice expressed more ICOS (p < 0.05), but less CD80 (p < 0.05).ConclusionThe content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells play a certain role in the process of regulating the immune response of T and B cells in the lung of Plasmodium-infected mice.

scholarly journals Characterization of γδT cells in lung of Plasmodium yoelii-infected C57BL/6 mice

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Haixia Wei ◽  
Chenxi Jin ◽  
Anping Peng ◽  
Hongyan Xie ◽  
Shihao Xie ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Post Infection ◽  
Plasmodium Yoelii ◽  
High Morbidity ◽  
Pathological Changes ◽  
Γδt Cells ◽  
Significant Difference ◽  
Ifn Γ ◽  
And Function

Abstract Background Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites. Methods Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. Results The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4+, IL-5+, IL-6+, IL-21+, IL-1α+, and IL-17+ γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3+ cells and absolute numbers of CD3+ cells, CD3+ CD4+ cells, CD3+ CD8+ cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3+ and CD3+ CD8+ cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69+, ICOS+, and CD80+ B cells between the WT infected and γδT KO infected mice (p > 0.05). Conclusions The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.

Activated CD4+ T cells enriched from spleen or colon induce apoptosis in intestinal epithellal cells via fas/fas ligand interactions

2001 ◽  
Vol 120 (5) ◽  
pp. A192-A192
Author(s):  
H TAKAISHI ◽  
T DENNING ◽  
K ITO ◽  
R MIFFLIN ◽  
P ERNST
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Ligand Interactions

scholarly journals Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT

2020 ◽  
Vol 11 ◽  
Author(s):  
Mahinbanu Mammadli ◽  
Weishan Huang ◽  
Rebecca Harris ◽  
Aisha Sultana ◽  
Ying Cheng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Treatment Strategies ◽  
Receptor Expression ◽  
Hematopoietic Stem ◽  
Target Organs ◽  
Donor T Cells ◽  
Inducible T Cell Kinase

Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without causing GVHD. Using murine models, we show that targeting IL-2-inducible T cell kinase (ITK) in donor T cells reduces GVHD while preserving GVL effects. Both CD8+ and CD4+ donor T cells from Itk-/- mice produce less inflammatory cytokines and show decrease migration to GVHD target organs such as the liver and small intestine, while maintaining GVL efficacy against primary B-cell acute lymphoblastic leukemia (B-ALL). Itk-/- T cells exhibit reduced expression of IRF4 and decreased JAK/STAT signaling activity but upregulating expression of Eomesodermin (Eomes) and preserve cytotoxicity, necessary for GVL effect. Transcriptome analysis indicates that ITK signaling controls chemokine receptor expression during alloactivation, which in turn affects the ability of donor T cells to migrate to GVHD target organs. Our data suggest that inhibiting ITK could be a therapeutic strategy to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.

scholarly journals Cellular and humoral peritoneal immunity to Mesocestoides vogae metacestode infection in mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Terézia Mačak Kubašková ◽  
Dagmar Mudroňová ◽  
Miroslava Vargová ◽  
Katarína Reiterová ◽  
Gabriela Hrčková
Keyword(s):  
T Cells ◽  
Cell Population ◽  
Peritoneal Cavity ◽  
Post Infection ◽  
Initial Increase ◽  
Mhc Ii ◽  
Cell Functions ◽  
Peritoneal Cells ◽  
Immunosuppressive Cell ◽  
Mesocestoides Vogae

Abstract Background Here, Mesocestoides (M.) vogae infection in mice is proposed as a suitable experimental model for studying the immunity in the peritoneal cavity of mice. Methods To investigate the kinetics of immune parameters in M. vogae-infected mice, we detected, using flow cytometry, the expression of selected lymphoid and myeloid markers within the peritoneal cell population at day 0, 3, 6, 10, 14, 19, 25, 30 and 35 post-infection. Then, using ELISA, we analyzed the cytokine IFN-γ, TGF-β, IL-4 and IL-10 responses and the levels of anti-M. vogae IgG and IgM antibodies in the peritoneal lavage fluid. Cells isolated from the peritoneal cavity were subjected to further molecular analysis. To assess cell activation, peritoneal cells were exposed to LPS, and culture supernatants were collected and assayed for the level of cytokines and production of nitrite. Ly6C+ and Ly6G+ cells were isolated using MACS from the peritoneal cells at day 35 post-infection. Both MACS-isolated subsets were co-cultured with preactivated T cells to measure their suppressive capacity. Next, the role of parasite excretory-secretory antigens in induction of CD11b+ myeloid cells with the suppressive phenotype and the production of IL-10 was examined. Results In the peritoneal cavity an initial increase of CD11b+Gr-1+F4/80highMHC IIhigh cells, NK, NKT cells and CD8+ cytotoxic T cells was observed in the first week of infection. At day 14 post-infection, an increase in the number of myeloid CD11b+Gr-1+ cells was detected, and most of this cell population expressed low levels of F4/80 and MHC II in later stages of infection, suggesting the impairment of antigen-presenting cell functions, probably through the excretory-secretory molecules. Moreover, we confirmed that peritoneal Gr1+ cells (Ly6C+ and Ly6G+ population) are phenotypically and functionally consistent with myeloid-derived suppressor cells. Metacestode infection elicited high levels of IL-10 and upregulated STAT-3 in peritoneal cells. A higher level of IgM suggests that this isotype may be predominant and is involved in the host protection. Conclusions Mesocestoides vogae tetrathyridia induced the recruitment of immunosuppressive cell subsets, which may play a key role in the downregulation of immune response in long-term parasitic diseases, and excretory-secretory antigens seem to be the main regulatory factor.

scholarly journals Evidence for the divergence of innate and adaptive T-cell precursors before commitment to the αβ and γδ lineages

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6591-6600 ◽  
Author(s):  
Jan Kisielow ◽  
Luigi Tortola ◽  
Jacqueline Weber ◽  
Klaus Karjalainen ◽  
Manfred Kopf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Negative Selection ◽  
Intraepithelial Lymphocytes ◽  
Lineage Commitment ◽  
Γδt Cells ◽  
Cell Lineages ◽  
Innate T Cells ◽  
Tcr Signals

Abstract In addition to adaptive T cells, the thymus supports the development of unconventional T cells such as natural killer T (NKT) and CD8αα intraepithelial lymphocytes (IELs), which have innate functional properties, particular antigenic specificities, and tissue localization. Both conventional and innate T cells are believed to develop from common precursors undergoing instructive, TCR-mediated lineage fate decisions, but innate T cells are proposed to undergo positive instead of negative selection in response to agonistic TCR signals. In the present study, we show that, in contrast to conventional αβT cells, innate αβT cells are not selected against functional TCRγ rearrangements and express TCRγ mRNA. Likewise, in contrast to the majority of γδT cells, thymic innate γδT cells are not efficiently selected against functional TCRβ chains. In precursors of conventional T cells, autonomous TCR signals emanating from the pre-TCR or γδTCR in the absence of ligand mediate selection against the TCR of the opposite isotype and αβ/γδ lineage commitment. Our data suggest that developing innate T cells ignore such signals and rely solely on agonistic TCR interactions. Consistently, most innate T cells reacted strongly against autologous thymocytes. These results suggest that innate and adaptive T-cell lineages do not develop from the same pool of precursors and potentially diverge before αβ/γδ lineage commitment.

scholarly journals Splenic Stroma-Educated Regulatory Dendritic Cells Induce Apoptosis of Activated CD4 T Cells via Fas Ligand-Enhanced IFN-γ and Nitric Oxide

2011 ◽  
Vol 188 (3) ◽  
pp. 1168-1177 ◽  
Author(s):  
Xiongfei Xu ◽  
Hai Yi ◽  
Zhenhong Guo ◽  
Cheng Qian ◽  
Sheng Xia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Ifn Γ ◽  
Regulatory Dendritic Cells

scholarly journals Immunological Reaction in TNF-α-Mediated Osteoclast Formation and Bone ResorptionIn VitroandIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hideki Kitaura ◽  
Keisuke Kimura ◽  
Masahiko Ishida ◽  
Haruka Kohara ◽  
Masako Yoshimatsu ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Metabolism ◽  
Stromal Cells ◽  
Fas Ligand ◽  
Bone Marrow Cells ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Bone Diseases

Tumor necrosis factor-α(TNF-α) is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF-αmay play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF-κB ligand (RANKL) to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF-αon bone metabolism may enable the identification of therapeutic targets that can efficiently suppress bone destruction in inflammatory bone diseases. TNF-αis considered to act by directly increasing RANK expression in macrophages and by increasing RANKL in stromal cells. Inflammatory cytokines such as interleukin- (IL-) 12, IL-18, and interferon-γ(IFN-γ) strongly inhibit osteoclast formation. IL-12, IL-18, and IFN-γinduce apoptosis in bone marrow cells treated with TNF-α  in vitro, and osteoclastogenesis is inhibited by the interactions of TNF-α-induced Fas and Fas ligand induced by IL-12, IL-18, and IFN-γ. This review describes and discusses the role of cells concerned with osteoclast formation and immunological reactions in TNF-α-mediated osteoclastogenesisin vitroandin vivo.

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