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Matthew R Collinson-Pautz, Kevin M Slawin, Jonathan M Levitt, David M Spencer
Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways...
2016: PloS One
Michiel C van Aalderen, Ester B M Remmerswaal, Kirstin M Heutinck, Anja Ten Brinke, Mariet C W Feltkamp, Neelke C van der Weerd, Karlijn A M I van der Pant, Frederike J Bemelman, René A W van Lier, Ineke J M Ten Berge
Polyomavirus BK (BKPyV) frequently reactivates in immunosuppressed renal transplant recipients (RTRs) and may lead to graft loss due to BKPyV-induced interstitial nephritis (BKVN). Little is known on the differentiation of CD8+ T cells targeting BKPyV in RTRs. Here we investigated whether BKPyV-specific CD8+ T cell differentiation differs in RTRs with varying degrees of BKPyV reactivation and/or BKVN. Using combinatorial encoding with tetramers carrying BKPyV major capsid protein (VP1) and large T antigen protein (LTAG) epitopes, we investigated CD8+ T cell responses to BKPyV in longitudinally obtained PBMC samples from 46 HLA-A02-positive RTRs and 20 healthy adults...
October 2016: PLoS Pathogens
Sanjay B Rathod, Anuradha S Tripathy
BACKGROUND AND AIM: Literature on the role of Regulatory T cells (Tregs) in acute viral infections is limited. Having established that the Tregs in self-limiting hepatitis E infection are elevated and functional, this study has focused on characterizing the specificity, phenotypes and identifying the molecules or factors responsible for enhancement of Treg cells and abrogation of Treg-mediated suppression in hepatitis E. METHODS: HEV rORF2p specific (a) Treg frequency, subset analysis and expression of surface and intracellular markers on Tregs and CFSE based functional analysis by flow cytometry (b) key cytokines quantification by multiplex (c) suppressive functional assay in the presence of anti-TGF-β1 or anti-IL-10 or both antibodies or Transwell insert or in combination were performed on samples from 58 acute patients (AVH-E), 45 recovered individuals from hepatitis E and 55 controls...
October 6, 2016: Human Immunology
Javier A Carrero, Stephen T Ferris, Emil R Unanue
Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets...
October 3, 2016: Current Opinion in Immunology
Fenne L Komdeur, Maartje C A Wouters, Hagma H Workel, Aline M Tijans, Anouk L J Terwindt, Kim L Brunekreeft, Annechien Plat, Harry G Klip, Florine A Eggink, Ninke Leffers, Wijnand Helfrich, Douwe F Samplonius, Edwin Bremer, G Bea A Wisman, Toos Daemen, Evelien W Duiker, Harry Hollema, Hans W Nijman, Marco de Bruyn
CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis...
September 16, 2016: Oncotarget
Morten Hansen, Mads Hald Andersen
Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8(+) T-cells and Th1 helper CD4(+) T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103(+) DCs, which have been shown to be experts in cross-priming and the induction of anti-tumor immunity...
September 16, 2016: Seminars in Immunopathology
Dallas B Flies, Tomoe Higuchi, Jaryse C Harris, Vibha Jha, Phyllis A Gimotty, Sarah F Adams
Although immune infiltrates in ovarian cancer are associated with improved survival, the ovarian tumor environment has been characterized as immunosuppressive, due in part to functional shifts among dendritic cells with disease progression. We hypothesized that flux in dendritic cell subpopulations with cancer progression were responsible for observed differences in antitumor immune responses in early and late-stage disease. Here we identify three dendritic cell subsets with disparate functions in the ovarian tumor environment...
August 2016: Oncoimmunology
Stefanie Trojandt, Iris Bellinghausen, Angelika B Reske-Kunz, Matthias Bros
Immature dendritic cells (iDCs) and tolerogenic DCs are essential for the induction and maintenance of peripheral tolerance. Tumors produce immuno-modulatory factors which imprint a pro-tolerogenic, maturation-resistant state in DCs. Here we asked for common markers of differentially tolerized human monocyte-derived DC populations. For this, PBMC-derived monocytes were differentiated to DCs in the presence of established immuno-modulators as released by tumors (IL-6, IL-10, TGF-ß, glucocorticoid [GC], prostaglandin E2 [PGE2])...
September 1, 2016: Human Immunology
Nicole Marquardt, Martin A Ivarsson, Erik Sundström, Elisabet Åkesson, Elisa Martini, Liv Eidsmo, Jenny Mjösberg, Danielle Friberg, Marius Kublickas, Sverker Ek, Gunilla Tegerstedt, Åke Seiger, Magnus Westgren, Jakob Michaëlsson
Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45(+) cells in AF is represented by a subset of fetal CD103(+) group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF...
September 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
M Rodriguez-Garcia, Z Shen, F D Barr, A W Boesch, M E Ackerman, J C Kappes, C Ochsenbauer, C R Wira
Dendritic cells (DCs) throughout the female reproductive tract (FRT) were examined for phenotype, HIV capture ability and innate anti-HIV responses. Two main CD11c(+) DC subsets were identified: CD11b(+) and CD11b(low) DCs. CD11b(+)CD14(+) DCs were the most abundant throughout the tract. A majority of CD11c(+)CD14(+) cells corresponded to CD1c(+) myeloid DCs, whereas the rest lacked CD1c and CD163 expression (macrophage marker) and may represent monocyte-derived cells. In addition, we identified CD103(+) DCs, located exclusively in the endometrium, whereas DC-SIGN(+) DCs were broadly distributed throughout the FRT...
August 31, 2016: Mucosal Immunology
Signe Tandrup Schmidt, Swapnil Khadke, Karen Smith Korsholm, Yvonne Perrie, Thomas Rades, Peter Andersen, Camilla Foged, Dennis Christensen
A prerequisite for vaccine-mediated induction of CD8(+) T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8(+) T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown to result in strong CD8(+) T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8(+) T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Lu Cheng, Huimin Jin, Yetao Qiang, Shuiyun Wu, Cheng Yan, Mutian Han, Tengfei Xiao, Nannan Yan, Huazhang An, Xiaoming Zhou, Qixiang Shao, Sheng Xia
Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice...
August 24, 2016: International Immunopharmacology
Szu-Wei Huang, Catherine Walker, Joanne Pennock, Kathryn Else, Werner Muller, Michael J D Daniels, Carolina Pellegrini, David Brough, Gloria Lopez-Castejon, Sheena M Cruickshank
Infection and injury of the gut are associated with cell damage and release of molecules such as extracellular ATP which is recognised by the purinergic P2X7 receptor (P2X7R). P2X7R is widely expressed in the gut by antigen presenting cells (APC) and epithelial cells, but the role of the P2X7R on epithelial cells is poorly understood. We investigated P2X7R in intestinal epithelium in vitro and in vivo using two model infections- Toxoplasma gondii and Trichinella spiralis. LPS and ATP treatment of intestinal epithelial cells and infection with T...
August 25, 2016: Immunology and Cell Biology
Heng Giap Woon, Asolina Braun, Jane Li, Corey Smith, Jarem Edwards, Frederic Sierro, Carl G Feng, Rajiv Khanna, Michael Elliot, Andrew Bell, Andrew D Hislop, Stuart G Tangye, Alan B Rickinson, Thomas Gebhardt, Warwick J Britton, Umaimainthan Palendira
Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation...
August 2016: PLoS Pathogens
Kim S LeMessurier, Yanyan Lin, Jonathan A McCullers, Amali E Samarasinghe
Influenza is a disease of the respiratory system caused by single stranded RNA viruses with varying genotypes. Immunopathogenesis to influenza viruses differs based on virus strain, dose, and mouse strain used in laboratory models. Although effective mucosal immune defenses are important in early host defense against influenza, information on the kinetics of these immune defense mechanisms during the course of influenza infection is limited. We investigated changes to antimicrobial peptides and primary innate immune cells at early time points after infection and compared these variables between two prominent H1N1 influenza A virus (IAV) strains, A/CA/04/2009 and A/PR/08/1934 in C57BL/6 mice...
September 2016: Antiviral Research
Cristian Doñas, Macarena Carrasco, Macarena Fritz, Carolina Prado, Gabriela Tejón, Francisco Osorio-Barrios, Valeria Manríquez, Paz Reyes, Rodrigo Pacheco, María Rosa Bono, Alejandra Loyola, Mario Rosemblatt
As it has been established that demethylation of lysine 27 of histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize that inhibition of JMJD3 may attenuate autoimmune disorders. We found that in vivo administration of GSK-J4, a selective inhibitor of JMJD3 and UTX, ameliorates the severity of experimental autoimmune encephalomyelitis (EAE). In vitro experiments revealed that the anti-inflammatory effect of GSK-J4 was exerted through an effect on dendritic cells (DCs), promoting a tolerogenic profile characterized by reduced expression of costimulatory molecules CD80/CD86, an increased expression of tolerogenic molecules CD103 and TGF-β1, and reduced secretion of proinflammatory cytokines IL-6, IFN-γ, and TNF...
August 12, 2016: Journal of Autoimmunity
Sertan Aksu, Eray Çalışkan, Yigit Cakiroglu
OBJECTIVE: To determine whether natural killer cell (NK) concentrations in the mid-secretory endometrial tissue of women with unexplained infertility differ from those in the mid-secretory endometrial tissue of fertile women. METHODS: This study was conducted with 22 patients with unexplained infertility caused by unsuccessful ovulation induced with gonadotrophins and 12 healthy fertile women, who formed a control group. Mid-secretory endometrial tissue samples were obtained with a Pipelle catheter, and the endometrial NK cell phenotypes were determined by flow cytometry...
September 2016: Journal of Reproductive Immunology
Peter D Krueger, Sowmya Narayanan, Fionna A Surette, Michael G Brown, Sun-Sang J Sung, Young S Hahn
The liver contains 2 transcriptionally distinct group 1 ILC subsets: CD49a(+) ILC1s and CD49b(+) NK cells. However, little is known about how group 1 ILCs contribute to hepatic immune responses. Therefore, we characterized murine liver-resident group 1 ILCs and found that CD49a(+) ILC1s express high levels of the inhibitory receptor NKG2A and localize near DCs in perivascular spaces surrounding the portal triads. Upon hepatic viral infection, NKG2A signaling in group 1 ILCs, especially in CD49a(+) ILC1s, inhibits CXCL9 expression required for robust accumulation of IFN-γ(+)CD49b(+) NK cells...
August 4, 2016: Journal of Leukocyte Biology
Phillip P Santoiemma, Carolina Reyes, Li-Ping Wang, Mike W McLane, Michael D Feldman, Janos L Tanyi, Daniel J Powell
OBJECTIVE: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Several factors prognostic for survival have been identified including the presence of certain lymphocyte markers. Tumor-infiltrating lymphocytes (TILs), particularly cytotoxic CD8+ TILs, have been shown to be most favorable for prognosis in ovarian cancer, although other immune cells including CD3+ T-cells, CD4+ T-cells, and B-cells have also demonstrated survival benefits. Although data for these markers exists, results are not uniform in the literature...
October 2016: Gynecologic Oncology
Luther A Bartelt, David T Bolick, Glynis L Kolling, James K Roche, Edna I Zaenker, Ana M Lara, Francisco Jose Noronha, Carrie A Cowardin, John H Moore, Jerrold R Turner, Cirle A Warren, Gregory A Buck, Richard L Guerrant
Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C...
July 2016: PLoS Neglected Tropical Diseases
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