bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human follicular dendritic cells interact with T cells via expression and regulation of cyclooxygenases and prostaglandin E and I synthases
Authors: Choe Jongseon , Lee In Yong , Cho Whajung , Kangwon Jini Kim. 
Published: June 2021

Prostaglandin E2 (PGE2) inhibits mature T cell proliferation and protects T cells from activation‐induced cell death (AICD). We have previously demonstrated that human follicular dendritic cells (FDC) strongly express prostaglandin I synthase (PGIS). In this study, the hypothesis that FDC have regulatory roles on germinal center (GC) T cells by controlling production of PGE2 and PGI2 was tested. Confocal microscopic analyses of human tonsil tissues revealed that FDC indeed expressed PGE synthase (PGES) in addition to PGIS. To confirm these results, we studied the regulation mechanism of prostaglandin production in FDC, utilizing an established human FDC‐like cell line, HK. Specifically in response to TNF‐α, TGF‐β, and LPS, protein expression of cyclooxygenase (COX)‐2 and downstream PGES was up‐regulated with coordinate kinetics while COX‐1 and PGIS were constitutively expressed. The increase of these enzymes was reflected in actual production of PGE2 and PGI2. Furthermore, the up‐regulation of PGE2 and PGI2 production was markedly down‐regulated by indomethacin and a selective COX‐2 inhibitor. PGI2 analog and PGE2 inhibited proliferation and AICD of T cells in dose‐ and time‐dependent manners. Finally, co‐culture experiments revealed that HK cells really inhibit proliferation and AICD of T cells. Put together, these results show an unrecognized pathway of FDC and T cell interactions and differential mechanisms for PGE2 and PGI2 production, suggesting an important implication for development and use of anti‐inflammatory drugs.This work was supported by the Korea Research Foundation Grant (MOEHRD, Basic Research Promotion Fund) (KRF‐2005‐041‐E00123) and the Vascular System Research Center grant from the Korea Science and Engineering Foundation.
Polycytokine responses by CD8+ T lymphocytes to KSHV/HHV8 lytic and latency proteins
Authors: Lepone Lauren , Knowlton Emilee , Rappocciolo Giovanna , Piazza Paolo , Jais Mariel , Rinaldo Charles 
Published: June 2021

Objectives: Based on our previous findings that dendritic cells (DC) are required to reveal epitopes of human herpesvirus 8 (KSHV/HHV8) glycoprotein B (gB) (Blood 99:3360, 2002), we determined CD8+ T cell responses to multiple lytic and latency viral proteins.Methods: T cells were stimulated with DC from HHV8 seropositive, HLA A*0201 donors that were loaded with overlapping peptides derived from gB and K8.1 lytic proteins, and K12 and LANA latency proteins, and screened for IFNγ production by ELISPOT. Positive peptides were then assessed for production of IFNγ, IL2, TNFα, MIP1β and CD107a by flow cytometry.Results: Our DC‐T cell model revealed 5 gB, 4 K8.1, 2 K12 and 5 LANA HLA A*0201 epitopes. The HHV8 lytic and latency proteins induced predominately IFN‐γ, IL2 and CD107a.Conclusions: This is the first demonstration that HHV8 lytic and latency proteins induce polycytokine production by CD8+ T cells. These targeted regions of the virus could be critical in HHV8 immunopathogenesis and vaccine development. (U01‐AI35041, R01 CA82053)
Effects of interferon‐γ and Francisella tularensis elicited soluble factors on macrophage antigen processing
Authors: Katkere Bhuvana , Wilson Justin E , Drake James R 
Published: June 2021

Francisella tularensis is an intracellular pathogen that survives and replicates within the cytoplasm of macrophages (MØ) upon escape from the phagosome. In interferon‐γ (IFN‐γ) activated MØ, F.tularensis is unable to escape the phagosome and is directed to the endosomal‐lysosomal degradation pathway. IFN‐γ also up‐regulates MHC class II expression, but it is as yet unclear how it influences MØ antigen processing. In a cell line where class II expression is under the control of an IFN‐γ non‐responsive promoter, it was observed that IFN‐γ activation results in changes in the antigen processing and presentation pathway, leading to altered the T‐cell activation and cytokine production. Furthermore, IFN‐γ suppresses the fluid‐phase antigen uptake, but fails to alter Fc‐receptor‐mediated antigen uptake. These results suggest that IFN‐γ differentially alters the antigen uptake, to target antigen for differential processing and presentation. Interestingly, supernatant from F. tularensis infected MØ contain one or more soluble factors, which suppresses fluid‐phase antigen uptake, perhaps to alter antigen processing and presentation to skew T‐cell responses.PO1 # AI‐056320
Two different human Th17 cells defined by chemokine receptor expression
Authors: Sato Wakiro , Aranami Toshimasa , Yamamura Takashi 
Published: June 2021

Objective: IL‐17‐producing CD4+ T cells (Th17 cells) have emerged as a T cell subset that may be pivotal in the pathogenesis of autoimmune diseases. We previously reported that human Th17 cells are distinct from Th1 cells in their chemokine receptor expression; Th17 cells as CCR2+CCR5−, whereas Th1 cells as CCR5+ (J. Immunol. 178:7525–7529, 2007). But other reports demonstrated that human Th17 cells are CCR4+CCR6+. We analyzed the relationship between the two populations.Method: Healthy human PBMCs (n = 6) were stained with CCR2, CCR4, CCR5 and CCR6 as well as CD45RA and CD4 and analyzed by FACS. CCR2+CCR5− and CCR4+CCR6+ memory CD4+ T cell subpopulations were sorted by FACS. Their IL‐17‐producing capacity was measured by ELISA.Result: The frequency of CCR2+CCR5− subpopulations within memory CD4+ T cells was 2.2+/−2.0%, whereas that of CCR4+CCT6+ was 16.8+/−6.9%. 24.7+/−8.8% of CCR2+CCR5− cells were CCR4+CCR6+, whereas only 3.0+/−2.5% of CCR4+CCR6+ cells were CCR2+CCR5−. The IL‐17 production level of both subpopulations was generally similar.Conclusion: CCR2+CCR5− cells and CCR4+CCR6+ cells basically do not overlap, suggesting that each population may function at different inflammatory conditions.
Novel NF‐κB‐mediated regulation of IFN‐α production by plasmacytoid dendritic cells upon stimulation of CpG‐A and CpG‐B
Authors: Cui Chongwei , Chung Eugene , George Thaddeus C , Singh Sukhwinder , Fitzgerald‐Bocarsly Patricia 
Published: June 2021

Two distinct types of CpG oligodeoxynucleotides have been identified that differ in their capacity to stimulate plasmacytoid dendritic cells (PDC): CpG‐A, but not CpG‐B, induces high amounts of IFN‐α, whereas CpG‐B induces PDC maturation. Here, we demonstrate that upon the inhibition of NF‐κB activation by SN50 or NBD, CpG‐B induced high amounts of IFN‐α, while CpG‐A‐induced IFN‐α was decreased. In addition, CpG‐B‐induced maturation was inhibited by NF‐κB inhibition. Using the new ImageStream imaging flow cytometry technology, we found that CpG‐B has a stronger ability to induce NF‐κB translocation in PDC than CpG‐A. Although both CpG‐A and CpG‐B‐induced NF‐κB translocation were inhibited by SN50, the inhibitory effect on CpG‐B‐induced translocation was more pronounced than with CpG‐A. Given this novel role for NF‐κB signaling in IFN‐α production, we tested whether there is a correlation between NF‐κB and IFN‐regulatory factor 7 (IRF‐7), the master regulator of IFN‐α production, activation. In contrast to the inability of CpG‐B to induce IRF‐7 translocation, we found that CpG‐A‐induced IRF‐7 translocation occurred at 5–6 hrs after stimulation. However, with the inhibition of NF‐κB translocation, CpG‐B induced high levels of IRF‐7 translocation after 1hr. These results suggest that NF‐κB plays an inverse role in the regulation of IFN‐α production by PDC upon stimulation with CpG‐A or CpG‐B.Supported by AI26806.
THE ROLE OF GRANULOCYTE‐MACROPHAGE COLONY STIMULATING FACTOR (GM‐CSF) IN TNBS‐COLITIS MODEL
Authors: Khajah Maitham Abbas , McCafferty Donna‐Marie 
Published: June 2021

Background: GM‐CSF is a hematopoietic cytokine that promotes neutrophil proliferation and maturation, promotes survival, and primes them for enhanced functions. It is produced by a variety of cell types including endothelial cellsand macrophages. Aim: in this study, we examined the role of GM‐CSF in a chemically‐induced model of colitis; 2,4,6‐trinitrobenzene sulphonic acid (TNBS). Methods: colitis was induced by a single intrarectal injection of TNBS(4mg, 20% ethanol) at day 1. Animals were treated with a single i.p injection of neutralizing anti‐GM‐CSF antibody (100μg/mouse) on day 1, or multiple injections on day 1,2,3, and 4, and killed on day 5 post‐induction of colitis. Control mice were injected with i.p NaCl. The role of GM‐CSF in neutrophil chemotaxis in vitro was also examined. Results: single injection of GM‐CSF antibody did not change the macroscopic score of inflammation and MPO activity between antibody treated and control mice. In contrast, by using multiple injections of GM‐CSF antibody, TNBS injection induced a significant increase in the macroscopic score of inflammation and colonic MPO activity in control mice, but mice treated with anti‐GM‐CSF antibody had a significantly reduced score. Real time‐PCR showed significantly enhanced mRNA expression of GM‐CSF in the colon at day 3 and 7 post‐induction of colitis compared to saline treated mice. A significant increase in WT neutrophil chemotaxis toward GM‐CSF was seen in the under‐agarose and the Boyden chamber assay. This neutrophil chemotactic response was PI3K dependent. Conclusion: 1‐GM‐CSF induces neutrophil chemotaxis in vitro through a PI3K‐dependent pathway. 2‐TNBS induces acute inflammation in mice in vivo, and GM‐CSF neutralization ameliorates colitis severity.3‐GM‐CSF may play a role in neutrophil recruitment to the gut.
Molecular effects to human regulatory T cells by treatment with T cell activation inhibitor and TNF blockade
Authors: Suzuki Katsuya , Setoyama Yumiko , Suzuki Miyuki , Keiko Yoshimoto , Kameda Hideto , Tsuzaka Kensei , Amano Koichi , Takeuchi Tsutomu 
Published: June 2021

Objective: Regulatory T cell (Treg) has a critical role for human autoimmunity. However, it has not been known how clinically effective therapeutic agents for autoimmune diseases, such as T cell activation inhibitor and TNF blockade affect to Treg in molecular level.Methods: Human CD4+T cells were purified and then co‐cultured with these agents (tacrolimus or infliximab) under anti‐CD3/CD28 antibody stimulation. The cells were harvested and FOXP3+Tregs and its related molecules were analyzed by flow cytometry. Next, DNA microarray analysis of CD4+CD25+CD127‐Treg by in vitro treatment was performed.Results: Tacrolimus significantly reduced CD62L low expressed inducible Tregs in dose dependent manner. In DNA microarray analysis, we have identified significantly up and down regulated 1,021 (tacrolimus) and 621 (infliximab) genes. Gene ontology analysis has also revealed significantly affected 15 gene groups, such as multicellular organismal process in both treatments.Conclusions: Immunological therapeutic intervention obviously affects to human peripheral Tregs in vitro. Its clinical significance should be required further studies in vivo.
Evaluation of proapototic transgenes to use in combination with Flt3L in an immune‐stimulatory gene therapy approach for Glioblastoma multiforme (GBM)
Authors: Candolfi Marianela , King Gwendalyn D , Muhammad AKM G , Puntel Mariana , Kroeger Kurt M , Liu Chunyan , Ahlsadeh Gabrielle E , Lerner Jonathan , Lee Sharon , Foulad David , Sato Katsuaki , Lowenstein Pedro R , Castro Maria G 
Published: June 2021

We showed that Flt3L recruits and activates APCs within GBM. We tested adenoviral vectors expressing pro‐apoptotic transgenes [HSV1‐thymidine kinase (Ad‐TK), TNF‐á (Ad‐TNF‐á), FasL (Ad‐FasL) or TRAIL (Ad‐TRAIL)], that would release tumor antigens to be up taken by APCs recruited by Ad‐Flt3L for GBM immunotherapy. Ad‐TK, Ad‐FasL and Ad‐TRAIL exerted GBM cell death in vitro, but only Ad‐TK and, at a lesser extent Ad‐FasL, improved survival of GBM‐bearing rats. Also, Ad‐TRAIL and Ad‐FasL were very neurotoxic, while Ad‐TK did not induce any side effects. Thus, we treated large intracranial GBM in rats with Ad‐TK+Ad‐Flt3L, which significantly improved survival and induced antitumor immunological memory. Ad‐TK+Ad‐Flt3L induced intratumoral recruitment of APCs with features of immature pDCs (CD3−, CD4+, CD45R+ cells that were CD86− and MHCII−). In summary, TK is a very safe and efficient pro‐apoptotic strategy to induce GBM regression when combined with Ad‐Flt3L. Our results warrant further development of this approach for human GBM Phase I trials.Support: NIH/NINDS R01 NS44556.01, R21‐NSO54143.01; UO1 NS052465.01; RO3 TW006273‐01 to M.G.C.; RO1 NS 054193.01; RO1 NS 42893.01; U54 NS045309‐01, and R21 NS047298‐01 to P.R.L; F32 NS058156.01 to M.C.
Cancer vaccine enhanced non‐tumor‐reactive CD8+ T cells exhibit a distinct molecular program associated with ‘division arrest anergy’
Authors: Beyer Marc , Mallmann Michael R. , Karbach Julia , Zander Thomas , Eggle Daniela , Classen Sabine , Debey‐Pascher Svenja , Jäger Elke , Schultze Joachim L. 
Published: June 2021

Vaccination of cancer patients against tumor antigens can induce peptide‐specific but non‐tumor‐reactive (NTR) CD8+ T cells. We used NY‐ESO‐1 peptide‐specific CD8+ T cell clones to assess the molecular programs associated with lack of tumor‐reactivity. TCR sequences revealed that NTR and tumor‐reactive (TR) T cells are derived from distinct progenitors. NTR T cells are characterized by low avidity TCRs and lack of NY‐ESO‐1 tetramer binding. Most striking, NTR T cells are characterized by a molecular program associated with division arrest anergy with elevated expression of the inhibitory molecule p27kip1, high expression of CD25, CD7, and CD69 and modulated expression of coreceptors. NTR T cells also exhibit elevated expression of inhibitory molecules and reduced levels of transcription factors responsible for T cell activation. In vivo monitoring of the NTR CD8+ T cell clone using a TCR‐specific PCR revealed high prevalence of NTR T cell clones with even increased levels during vaccination.In vivo expansion of NTR T cells that can only be quantified by combining classical T cell cloning approaches with quantitative PCR adds another level of complexity to tumor host interaction. Certainly, these novel findings need to be considered when developing future adoptive T cell transfer approaches and cancer vaccines.Research support: Sofja Kovalevskaja Award (Alexander von Humboldt‐Foundation)
Role of CD30/CD30L Mediated Signaling in the Cross‐talk of Natural Killer Cells and Dendritic Cells
Authors: Simhadri Vijaya Lakshmi , Hansen Hinrich P , Simhadri Venkateswara Rao , Reiners Katrin , Engert Andreas , Von Strandmann Elke Pogge 
Published: June 2021

Natural killer (NK) cells are involved in innate immunity and also contribute to adaptive immunity, mediated through the cross‐talk with immature dendritic cells (iDCs). NK cells and iDCs play a major role at the site of inflammation. The activation of NK cells and maturation of iDCs is partially characterized on the molecular level, depends on the release of proinflammatory cytokines and receptor‐ligand interactions.Activated NK cells express CD30, and its ligand CD30L (CD153) is expressed on iDCs. We describe that engagement of CD30L contributes to the activation and maturation of dendritic cells.Stimulation of monocyte derived iDCs with immobilized CD30‐Fc results in the release of pro‐inflammatory cytokines TNFalpha, IL‐6 and IL‐8, and can be blocked by CD30 antibodies. Engagement of CD30L on iDCs leads to Reactive Oxygen Species (ROS) signaling; and the release of TNFalpha is blocked by MAP kinase inhibitors. Intriguingly, the interaction induced the expression of CD83, a specific marker for mature dendritic cells. We postulate that CD30‐CD30L interaction contributes to DC‐maturation, based on the induction of cytokine release.The better understanding of the molecules involved in the NK‐DC cross‐talk will provide a basis for the development of immunotherapeutics modulating the activity of NK cells and DCs.Research was supported by Deutsche Forschungsgemeinschaft (DFG) (STR 530/5‐1).
Sugar‐sweetened beverages consumption is associated with BMI in Mexican adolescents. National Health and Nutrition Survey‐2006
Authors: Jiménez Alejandra , Flores Mario , Shamah Teresa 
Published: June 2021

The objective was to evaluate the association between consumption of sugar‐sweetened beverages (SSBs) and body mass index (BMI) in Mexican adolescents.Data from the National Health and Nutrition Survey‐2006 of Mexico were analyzed. Consumption of SSBs (i.e: sodas, fruit juices and sweet‐flavored drinks) was evaluated by means of a semi‐quantitative food frequency questionnaire. BMI was calculated as weight in kg/height in mt squared.Information on socio‐demographic characteristics, sexual maturity, parents′ obesity, physical activity and inactivity (i.e: TV‐watching) during the week before the interview, was also obtained.A total of 10,689 participants who represented 10,029,247 Mexican adolescents 10 to 19 y (mean age 13.8 ± 2.7 y) were evaluated. 50.4% were females. Mean time spent watching TV was 7.5 ± 5.5 h/week. Mean time of moderate and intense activity was 6.0 ± 4.0 h/week.Mean BMI was 21.4 ± 4.4. The median consumption of SSBs was 1.08 (0.76,1.43) servings per day, after adjusting by energy intake, age, sex, physical activity, TV‐watching and socioeconomic level.Multiple‐linear regression analysis showed that, for each portion of sodas consumed, a 0.20 ‐point increase in BMI was observed in males (p<0.05), after adjusting for confounders.It was concluded that consumption of sodas is positively associated with BMI in Mexican male adolescents.Supported by Ministery of Health, Mexico.
In vitro effects of arginine or citrulline associated with a statine on nitrite oxide (NO) production in bovine aortic endothelial cells (BAECs)
Authors: Berthe Marie‐Clotilde , Bernard Mélisande , Darquy Sylviane , Couderc Rémy , Cynober Luc 
Published: June 2021

Introduction Endothelial dysfunction occured very early in atherogenesis. It is due to decrease in NO production by endothelial cells leading to loss of vasodilation. NO is synthetised in endothelial cells by the endothelial nitric oxide synthase (eNOS) from arginine, with production of citrulline. Citrulline can be recycled in arginine, via arginino succinate synthase (ASS) and arginino succinate lyase (ASL). Moreover, statine increases eNOS activity and synthesis and therefore improves endothelial function.Materials and methods NO was determined using a nitrate and nitrite fluorimetric assay.ResultsNO production was increased in the presence of simvastatine and arginine or citrulline. This increase was more important with arginine compared to citrulline at 1mM. Without any substrate in the medium, an increase in eNOS protein level was found. In the presence of arginine 1mM, the simvastatine effect on eNOS protein level was more pronounced than in the presence of arginine 0,5mM. The effect was found also in the presence of citrulline 1mM. The same results were observed with eNOS mRNA level. Finally, when cells were incubated with arginine 0,5mM, simvastatine lead to increase ASL and ASS mRNA expression.ConclusionThe association of substrate with simvastatine induces an increase NO production, compared with arginine or citrulline or statine only, which is in agreement with the increase in BAECs of eNOS mRNA and protein levels.
Maximizing protein anabolism in young and aging muscle: a dose response to dietary protein ingestion
Authors: Symons T. Brock , Sheffield‐Moore Melinda , Wolfe Robert R. , Paddon‐Jones Douglas 
Published: June 2021

We have recently shown that a single moderate serving of a protein‐rich food (113 g of lean beef; 30 g protein) acutely increases muscle protein synthesis by 51% in both young and elderly.PURPOSE:To quantify the age‐ and dose‐response to nutrient ingestion by measuring muscle protein synthesis following a single large serving of a protein‐rich food (340 g lean beef; 90 g protein; ~1.2g/kg/day for 70kg individual) in young (n=7; 29±3yrs) and elderly (n=7; 66±2yrs) individuals.METHODS:Venous blood and vastus lateralis muscle biopsy samples were obtained during a primed (2.0 μmol/kg) constant infusion (0.08 μ mol·kg−1min−1) of L‐ [ring‐13C6] phenylalanine. Mixed muscle fractional synthesis rate (FSR) was calculated during a 3 h post‐absorptive period and for 5 h following ingestion of 340 g of 90% lean ground beef.RESULTS:Mixed muscle FSR increased by approximately 46% in both the young (pre: 0.082±0.010; post: 0.119±0.012) and the elderly (pre: 0.086±0.008; post: 0.125±0.014 %/h) following ingestion of 340 g of lean beef. These data were similar to the response to ingestion of 113 g lean beef in the young (pre: 0.074±0.005; post: 0.113±0.005 %/h) and elderly (pre: 0.072±0.004; post: 0.108±0.006).CONCLUSION:A large serving of protein increases muscle protein synthesis by 46% in both young and elderly, but provides no additional anabolic stimulus above that afforded by a more moderately sized 113 g serving. These data have implications for the dose and distribution of dietary protein over the course of a day.
The National Mindless Eating Challenge: Dietary Profiles Predict a Differential Effectiveness of Interventions:
Authors: Wansink Brian 
Published: June 2021

While dieters may differ, dietary advice too often does not. There were two purposes of this study: 1) Develop a diagnostic means of segmenting dieters, and 2) determine which empirically‐based diet tips are most successful with which segments. The participants consisted of 2500 individuals who had joined the web‐based National Mindless Eating Challenge, expressing an interest in losing weight. After obtaining self‐reported pretest measures of weight and wellness, participants were randomly given three of 30 environmental diet changes (e.g., use smaller bowls, don't serve family style, and so on) that have been empirically suggested to reduce serving sizes or serving frequency.A majority of dieters lost more weight than those in a face‐to‐face high‐intervention control group. What is remarkable, however, is while some clusters of tips proved to be successful for some segments, other clusters of tips were more successful for other segments. These segmentation differences underscore why many interventions appear to have generally low power: their impact is diffused because it is inappropriate for other segments of dieters.