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https://www.readbyqxmd.com/read/28424687/cd103-cd8-t-cells-in-the-toxoplasma-infected-brain-exhibit-a-tissue-resident-memory-transcriptional-profile
#1
Tyler A Landrith, Suhas Sureshchandra, Andrea Rivera, Jessica C Jang, Maham Rais, Meera G Nair, Ilhem Messaoudi, Emma H Wilson
During chronic infection, memory T cells acquire a unique phenotype and become dependent on different survival signals than those needed for memory T cells generated during an acute infection. The distinction between the role of effector and memory T cells in an environment of persistent antigen remains unclear. Here, in the context of chronic Toxoplasma gondii infection, we demonstrate that a population of CD8 T cells exhibiting a tissue-resident memory (TRM) phenotype accumulates within the brain. We show that this population is distributed throughout the brain in both parenchymal and extraparenchymal spaces...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28423340/transforming-growth-factor-%C3%AE-signaling-in-regulatory-t-cells-controls-t-helper-17-cells-and-tissue-specific-immune-responses
#2
Joanne E Konkel, Dunfang Zhang, Peter Zanvit, Cheryl Chia, Tamsin Zangarle-Murray, Wenwen Jin, Songlin Wang, WanJun Chen
Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue environments and against many inflammatory insults, yet the tissue-enriched factor(s) that influence Treg cell phenotype and function remain largely unknown. We have shown a vital role for transforming growth factor-β (TGF-β) signals in safe-guarding specific Treg cell functions. TGF-β signals were dispensable for steady-state Treg cell homeostasis and for Treg cell suppression of T cell proliferation and T helper-1 (Th1) cell differentiation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28423181/mesenteric-lymph-node-cd11b-cd103-pd-l1-high-dendritic-cells-highly-induce-regulatory-t-cells
#3
Aya Shiokawa, Ryutaro Kotaki, Tomohiro Takano, Haruyo Nakajima-Adachi, Satoshi Hachimura
Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3(+) regulatory T cells to regulate immune responses to beneficial or non-harmful agents in the intestine, such as commensal bacteria and foods. Several studies in MLN DCs have revealed that CD103(+) DC subset highly induces regulatory T cells, and another study has reported that MLN DCs from PD-L1-deficient mice could not induce regulatory T cells. Thus, the present study investigated expression of these molecules on MLN CD11c(+) cells. Four distinct subsets expressing CD103 and/or PD-L1 were identified, namely CD11b(+) CD103(+) PD-L1(High) , CD11b(-) CD103(+) PD-L1(High) , CD11b(-) CD103(+) PD-L1(Low) , and CD11b(+) CD103(-) PD-L1(Int...
April 19, 2017: Immunology
https://www.readbyqxmd.com/read/28418282/immunohistochemical-detection-of-hairy-cell-leukemia-in-paraffin-sections-the-role-of-pax5-and-cd103-double-staining-to-improve-specificity-and-sensitivity
#4
Igor B Rozenvald, Maurice D Richardson, Lenessa Brock, Russell L Maiese
CONTEXT: - In hematopathology practice, abnormal expression of CD103 on B cells is detected by flow cytometry in hairy cell leukemia (HCL) and, in combination with other phenotypic and morphologic findings, provides diagnostic specificity and sensitivity. Immunostaining on paraffin sections makes it possible to perform immunophenotyping in situ. However, normal bone marrow contains CD103-positive cells, which are not B cells, making it difficult to be certain about low-level involvement by HCL...
April 18, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28412591/baseline-%C3%AE-catenin-programmed-death-ligand-1-expression-and-tumour-infiltrating-lymphocytes-predict-response-and-poor-prognosis-in-braf-inhibitor-treated-melanoma-patients
#5
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407741/the-pd-1-pd-l1-pathway-promotes-development-of-brain-resident-memory-t-cells-following-acute-viral-encephalitis
#6
Sujata Prasad, Shuxian Hu, Wen S Sheng, Priyanka Chauhan, Amar Singh, James R Lokensgard
BACKGROUND: Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bTRM) following murine cytomegalovirus (MCMV) infection. METHODS: Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8(+) T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bTRMs...
April 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28405506/oral-delivery-of-tumor-microparticle-vaccines-activates-nod2-signaling-pathway-in-ileac-epithelium-rendering-potent-antitumor-t-cell-immunity
#7
Wenqian Dong, Huafeng Zhang, Xiaonan Yin, Yuying Liu, Degao Chen, Xiaoyu Liang, Xun Jin, Jiadi Lv, Jingwei Ma, Ke Tang, Zhuowei Hu, Xiaofeng Qin, Bo Huang
Exploiting gut mucosal immunity to design new antitumor vaccination strategy remains unexplored. Tumor cell-derived microparticles (T-MP) are natural biomaterials that are capable of delivering tumor antigens and innate signals to dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs by oral vaccination route effectively access and activate mucosal epithelium, leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs generated potent inhibitory effect against the growth of B16 melanoma and CT26 colon cancer in mice, which required both T cell and DC activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28380351/local-inflammatory-cues-regulate-differentiation-and-persistence-of-cd8-tissue-resident-memory-t-cells
#8
Tessa Bergsbaken, Michael J Bevan, Pamela J Fink
Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm) cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8(+) T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103(-)CD69(+) Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN)-β and interleukin-12 (IL-12), which regulated Trm markers, including CD103...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28378805/neonatal-mice-possess-two-phenotypically-and-functionally-distinct-lung-migratory-cd103-dendritic-cell-populations-following-respiratory-infection
#9
T J Ruckwardt, K M Morabito, E Bar-Haim, D Nair, B S Graham
The CD103(+) subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8(+) T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103(+) DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103(+) DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103(+) DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28355562/th1-differentiation-drives-the-accumulation-of-intravascular-non-protective-cd4%C3%A2-t-cells-during-tuberculosis
#10
Michelle A Sallin, Shunsuke Sakai, Keith D Kauffman, Howard A Young, Jinfang Zhu, Daniel L Barber
Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73(+)CXCR3(+)T-bet(dim) stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL- 12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1(+)KLRG1(+) Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#11
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28337201/phenotype-and-tissue-residency-of-lymphocytes-in-the-murine-oral-mucosa
#12
Joo-Young Park, Hyunsoo Chung, Youngnim Choi, Jung-Hyun Park
The oral mucosa is a critical barrier tissue that harbors a series of distinct immune cell subsets. Immune surveillance in the oral mucosa is important for both local and systemic immunity because the oral cavity is a heavily utilized route of pathogen entry and also serves as site of pathogen propagation. Nonetheless, composition and phenotype of the lymphocyte pool in the oral mucosa have remained poorly characterized. Utilizing a newly established protocol for mucosal immune cell isolation, here, we report that the oral mucosa features a unique cellular composition of immune cells, which differed not only from secondary lymphoid organs but also from mucosal tissues in the gut and lung...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28316599/interleukin-4-inhibits-regulatory-t-cell-differentiation-through-regulating-cd103-dendritic-cells
#13
Lei Tu, Jie Chen, Hongwei Zhang, Lihua Duan
CD103+ dendritic cells (DCs) have been shown to play a crucial role in the pathogenesis of inflammatory bowel diseases (IBDs) through educating regulatory T (Treg) cells differentiation. However, the mechanism of CD103+ DCs subsets differentiation remains elusive. Interleukin (IL)-4 is a pleiotropic cytokine that is upregulated in certain types of inflammation, including IBDs and especially ulcerative colitis. However, the precise role of IL-4 in the differentiation of CD103+ DCs subpopulation remains unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28295019/m2e-tetramer-specific-memory-cd4-t-cells-are-broadly-protective-against-influenza-infection
#14
D G Eliasson, A Omokanye, K Schön, U A Wenzel, V Bernasconi, M Bemark, A Kolpe, K El Bakkouri, T Ysenbaert, L Deng, W Fiers, X Saelens, N Lycke
Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A(d) restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28286160/p2x7-receptor-promotes-intestinal-inflammation-in-chemically-induced-colitis-and-triggers-death-of-mucosal-regulatory-t-cells
#15
Vanessa R Figliuolo, Luiz Eduardo Baggio Savio, Hanaa Safya, Hayandra Nanini, Cláudio Bernardazzi, Alessandra Abalo, Heitor S P de Souza, Jean Kanellopoulos, Pierre Bobé, Cláudia M L M Coutinho, Robson Coutinho-Silva
P2X7 receptor activation contributes to inflammation development in different pathologies. We previously reported that the P2X7 receptor is over-expressed in the gut mucosa of patients with inflammatory bowel disease, and that P2X7 inhibition protects against chemically induced colitis. Here, we investigated in detail the role of the P2X7 receptor in inflammatory bowel disease development, by treating P2X7 knockout (KO) and WT mice with two different (and established) colitis inductors. P2X7 KO mice were protected against gut inflammation induced by 2,4,6-trinitrobenzenesulfonic acid or oxazolone, with no weight loss or gut histological alterations after treatment...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28276457/cd40-signalling-abrogates-induction-of-ror%C3%AE-t-treg-cells-by-intestinal-cd103-dcs-and-causes-fatal-colitis
#16
Christian Barthels, Ana Ogrinc, Verena Steyer, Stefanie Meier, Ferdinand Simon, Maria Wimmer, Andreas Blutke, Tobias Straub, Ursula Zimber-Strobl, Esther Lutgens, Peggy Marconi, Caspar Ohnmacht, Debora Garzetti, Bärbel Stecher, Thomas Brocker
Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103(+) dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt(+) (RORγt(+)) Helios(-)-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103(+) DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103(+) DCs in LP and a low frequency of RORγt(+)Helios(-) iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262752/highly-exposed-hiv-1-seronegative-female-commercial-sex-workers-sustain-in-their-genital-mucosa-increased-frequencies-of-tolerogenic-myeloid-and-regulatory-t-cells
#17
V Thibodeau, L Fourcade, A-C Labbé, M Alary, F Guédou, J Poudrier, M Roger
We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261866/morphologic-and-immunophenotypic-features-of-hairy-cell-leukemia-involving-lymph-nodes-and-extranodal-tissues
#18
Jacqueline M Cortazar, Daniel J DeAngelo, Geraldine S Pinkus, Elizabeth A Morgan
Hairy cell leukemia (HCL) is a rare B-cell neoplasm that mainly affects bone marrow (BM), peripheral blood (PB), and spleen. Involvement of lymph nodes and extranodal structures is considered infrequent. Herein we describe our institutional experience of nodal (n=10) and extranodal (n=3) HCL over a thirty-year period. Ten patients had prior evidence of HCL within the BM or PB at a median 35.8 months before nodal/extranodal diagnosis (range, <1 to 175 months), and HCL was diagnosed concurrently within the bone marrow of 1 additional patient...
March 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28261667/protein-malnutrition-modifies-innate-immunity-and-gene-expression-by-intestinal-epithelial-cells-and-human-rotavirus-infection-in-neonatal-gnotobiotic-pigs
#19
Anastasia N Vlasova, Francine C Paim, Sukumar Kandasamy, Moyasar A Alhamo, David D Fischer, Stephanie N Langel, Loic Deblais, Anand Kumar, Juliet Chepngeno, Lulu Shao, Huang-Chi Huang, Rosario A Candelero-Rueda, Gireesh Rajashekara, Linda J Saif
Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets...
March 2017: MSphere
https://www.readbyqxmd.com/read/28261212/%C3%AE-2%C3%A2-1-fructans-modulate-the-immune-system-in-vivo-in-a-microbiota-dependent-and%C3%A2-independent-fashion
#20
Floris Fransen, Neha M Sahasrabudhe, Marlies Elderman, Margaret Bosveld, Sahar El Aidy, Floor Hugenholtz, Theo Borghuis, Ben Kousemaker, Simon Winkel, Christa van der Gaast-de Jongh, Marien I de Jonge, Mark V Boekschoten, Hauke Smidt, Henk A Schols, Paul de Vos
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples...
2017: Frontiers in Immunology
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