bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of human corneal resident cells on the immune modulation of CD4 T cells (49.19)
Authors: Ryu Jin Suk , Jeong Hyun Jeong , Lee Young Eun , Kim Mee Kum , Wee Won Ryang 
Published: January 2023

Abstract
Fibroblasts which are terminally differentiated stromal cells have been reported to share immunosuppressive effect on the lymphocyte activation with mesenchymal stem cells. However, the immunomodulatory role of the corneal residential stromal cells(keratocytes) have not been known. We investigated the immunomodulatory effect of human keratocytes on the CD4+ T cells as a part of ocular immune privilege. The study was performed in accordance with the guidelines of the Declaration of Helsinki. Human peripheral blood mononuclear cells were obtained from the healthy voluntary donors with informed consents. CD4+ T cells were purified through MACS separator with the human CD4+ T Cell Isolation Kit II (Miltenyi Biotec). The human keratocytes were collected from the remaining donor graft. CFSE stained CD4+ T cells were stimulated with anti-CD3/CD28, and were then co-cultured with keratocytes with or without 1-methyltryptophan. The proliferation of T cells and the secretion of IFN-γ were evaluated. Changes of cytokine expression were also evaluated using ELISA after co-culture. We found that keratocytes suppressed the proliferation and the secretion of IFN-γ of CD4 T cells, and enhanced IL-10 and TGF-β, which were partially reversed with 1-methyltryptophan treatment. It implied that human keratocytes might have an immune modulatory effect on the CD4 T cells through indoleamine 2,3 dioxygenase-dependent in part, which seemed likely to contribute to ocular immune privilege.
Influenza infection generates memory CD4 T cells that occupy a specific lung resident niche and mediate early in situ responses (49.21)
Authors: Turner Damian , Bickham Kara , Thome Joseph , Yudanin Naomi , Farber Donna 
Published: January 2023

Abstract
Lung-resident T cells are uniquely poised to mediate early in situ responses to respiratory pathogens. We have previously identified a subset of lung-resident CD4 T cells that mediate optimal protective immunity to respiratory infection. Here, we have examined the mechanisms for the establishment of lung-resident memory CD4 T cells and their role in anti-viral responses. Using intravenous (iv) infusion of antibody to differentiate between cells in the lung interstitium and those accessible to the circulation, we discovered that a minor subset of lung αβ CD4 T and most γδ T cells are protected from iv antibody staining (protected subset) while the remaining αβ CD4 T cells are readily stained (accessible subset). The protected αβ CD4 T cell subset and γδ T cells similarly expressed increased levels of CD11a, CD69, CD103 and CCR6 as compared to the accessible subset. The protected population of αβ CD4 T cells is established through respiratory infection as it comprises less than 10% of αβ CD4 T cells in naïve animals but represents approximately 30% of lung cells in influenza immune mice during the memory stage. Once established, the protected memory αβ CD4 T cells along with γδ T cells produces IFN-γ and IL-17 in situ early after influenza rechallenge. Our results show that the lung CD4 T cell population is comprised of a circulating subset and a tissue-resident subset with the tissue resident αβ CD4 T and γδ T cells acting as early responders to respiratory infections.
Hallmarks of adaptive immunity in γδ T cells following oral Listeria infection (49.7)
Authors: Sheridan Brian , Pham Quynh-Mai , Fu Han-Hsuan , Schubert Wolf-Dieter , Freitag Nancy , Lefrancois Leo 
Published: January 2023

Abstract
Traditionally, γδ T cells have been thought of as an arm of the innate immune system. Our findings suggest that γδ T cells also have an important role in adaptive immunity and anamnestic responses. The ability of γδ T cells to generate bona-fide memory populations has not been well established. Surprisingly, oral Listeria monocytogenes (L.m.) infection induced a unique population of γδ T cells in the mesenteric lymph nodes and lamina propria that was maintained into immunologic memory. They were mobilized into the blood and upregulated the gut homing receptor α4β7. This adaptive γδ T cell response differs from innate γδ T cells in their function, proliferation, and Vγ usage. The responding mucosal γδ T cell subset was comprised of both IL-17A and IFNγ producers. Notably, all cytokine production was limited to γδ T cells which did not express CD27 suggesting distinct regulation of cytokine production by adaptive γδ T cells. This population expanded more rapidly and more robustly to a secondary oral L.m. infection but not to a secondary intravenous L.m. infection or a secondary oral Salmonella infection suggesting contextual specificity to the priming pathogen. Further, this population is capable of providing protection in collaboration with αβ T cells following secondary oral challenge demonstrating their physiologic significance in vivo. Thus, γδ T cells are capable of generating a bona-fide immunologic memory population following oral L.m. infection.
Effective prevention and treatment of CD8 T cell-mediated graft-versus-host-like disease (GvHD) using a JAK inhibitor. (51.3)
Authors: Okiyama Naoko , Furumoto Yasuko , Villarroel Vadim , Gutermuth Jan , Ghoreschi Kamran , Gadina Massimo , Katz Stephen 
Published: January 2023

Abstract
A Janus kinase (JAK) inhibitor, tofacitinib (tofa), inhibits JAK 1, 2 and 3 of some cytokine receptor pathways, affects CD4+ T cell respnses, and is being tested in more than 20 clinical trials in autoimmune diseases.To determine if tofa affects CD8+ T cells, we analyzed its effect on a CD8+ T-cell-dependent murine model of GvHD (OT-I T cell transfer into Tg mice expressing ovalbumin (OVA) in their skin and mucosae). Tofa at 50 mg/kg/day (50) p.o. completely prevented GvHD development in our model vs. vehicle-treated mice with final weights: -0.6%±5.6 and -15.4%±4.1 (p&lt;0.01; 2-way ANOVA) and clinical scores: 0 and 7.3±0.52 (p&lt;0.01; U test) 13 days post OT-I cell transfer. Mice treated with tofa 50 starting at day 5 were completely rescued, with no clinical signs of GVHD. FACS analysis demonstrated reduced expression of OVA-specific TCR and reduced activation of OT-I cells in skin-draining lymph nodes from mice transferred with GFP/OT-I cells and treated with tofa 50 vs. vehicle alone. Tofa inhibited proliferation of OT-I cells stimulated by SIINFEKL (OVA peptide) in vitro. qRT-PCR showed increased chemokine mRNA (CXCL9; 39-fold and CXCL10; 22-fold) in the epidermis of vehicle-treated mice vs. tofa 50-treated mice 4 days post OT-I cell transfer. The effect of tofa could be explained by its inhibition of JAK signaling in IL-2 and IL-15 receptor-pathways of OT-I cells and in IFN-γ receptor-pathways of keratinocytes and tofa may thereby be effective in autoimmune diseases.
Dietary fish oil results in a microenvironment with high anti-inflammatory potential, but does not inhibit mice from mounting an effective immune response to Borrelia burgdorferi. (51.9)
Authors: Cunningham Anna , Dumlao Darren , Wax Laura , Norris Paul , Hughes-Hanks Jennifer , Halpin Rachel , Lett Kawasi , Blaho Victoria , Mitchell William , Fritsche Kevin , Dennis Edward , Brown Charles 
Published: January 2023

Abstract
Dietary fish oil is suggested to alleviate a variety of inflammatory disorders by altering eicosanoid production. However, the extent of changes resulting from a diet high in omega-3 fatty acids is unknown, and any benefits resulting from these changes are unsubstantiated. Several studies conclude that the lack of phenotypic effects of fish oil result from an inability to consume sufficient quantities for any benefits to be evident. We fed mice either a control diet containing 18% by weight soybean oil or fish oil and infected the mice with Borrelia burgdorferi in order to quantify changes in temporal eicosanoid production throughout the course of disease. Using a lipidomics approach, we detected dramatic temporal and compositional changes in the majority of the 103 eicosanoids monitored. LOX metabolites produced in fish oil-fed mice were primarily generated non-enzymatically, and arachidonic acid metabolism was shunted from PGE2 synthesis to PGD2 synthesis resulting in the production and accumulation of 15d-PGJ2. Despite the fact that the fish oil diet led to a highly anti-inflammatory microenvironment, mice were able to mount an immune response and clear infection as well as mice fed a control diet. This study confirms that a diet high in fish oil results in a microenvironment with high anti-inflammatory potential but does not necessarily affect the ability of the organism to mount an effective immune response to infection with Borrelia burgdorferi.
Vaccine Dose Alters Immunodominant Epitopes and Cytokine Profile in Response to the Acinetobacter baumannii rOmpA Vaccine (52.12)
Authors: Lin Lin , Baquir Beverlie , Tan Brandon , Ho Tiffany , Pantapalangkoor Paul , Hujer Kristine , Bonomo Robert A. , Spellberg Brad 
Published: January 2023

Abstract
Background: The rOmpA vaccine protects mice from lethal infection caused by extreme-drug-resistant (XDR) Acinetobacter baumannii. The role of dose and epitope in immunology of the rOmpA vaccine was explored. Methods: The rOmpA vaccine was epitope-mapped using overlapping peptides to stimulate splenocytes from mice administered varying vaccine doses. B cell epitopes were mapped by peptide immunoblotting. Results: Vaccination with rOmpA plus Al(OH)3 adjuvant induced IFN-γ, IL-4, and IL-17+ splenocytes. Epitope mapping revealed distinct T cell epitopes that induced IFNγ+, IL-4+, and IL-17A+ splenocytes. B cell and T cell epitopes had only partial overlap, and the overlapping epitopes induced more potent IL-4 responses from splenocytes than IFN-γ responses. More than twice as many peptides induced IFN-γ, IL-4, and IL-17 responses when used to active splenocytes from high dose (100 µg) vaccinated mice versus low dose (3 µg) vaccinated mice. The IFN-γ:IL-4 ratios induced by each peptide varied depending on the dose of whole protein used to vaccinate the mice. Conclusions: rOmpA dose alters the epitope profile of responding lymphocytes, with higher vaccine doses resulting in epitope spreading. Furthermore, each individual epitope may stimulate a different cytokine profile from responding lymphocytes depending on the dose of vaccine used to immunize the mice.
Pattern recognition receptor SRA/CD204 restricts T cell activation and antitumor immunity (52.13)
Authors: Wang Xiang-Yang , Yi Huanfa , Yu Xiaofei , Guo Chunqing , Qian Jie , Zuo Daming , Subjeck John 
Published: January 2023

Abstract
Scavenger receptor A (SRA), also termed CD204, is an innate immune receptor primarily expressed in dendritic cells (DCs) and macrophages, and displays a broad ligand-binding specificity. SRA/CD204 has been implicated in multiple physiological and pathological processes, including atherosclerosis, Alzheimer's disease, and host defense against pathogen infection. Although initial studies identified SRA/CD204 as a binding receptor for large heat shock proteins (HSPs), our subsequent studies revealed an unexpected feature of SRA/CD204 in attenuating antitumor immune response generated by vaccines formulated with adjuvants of mammalian and foreign origins. SRA/CD204 is capable of dampening both Th1 and CTL responses by limiting the intrinsic immunogenicity of DCs during interactions with T cells. SRA/CD204 may also serve as a molecule bridging antigen-presenting cells (APCs) and activated T cells for immune regulation. Dual effects-mediated by SRA/CD204 indicate pleiotropic functions of this molecule in regulating immune homeostasis and host defense. Furthermore, genetic manipulation of SRA/CD204 expression markedly enhances the immunostimulatory activities of DCs in driving antigen-specific T cell immunity, leading to profoundly improved control of tumor and metastases in preclinical models. Therefore, our studies also provide a rationale for improving vaccine potency and cancer immunotherapy through SRA/CD204-targeting approaches.
Glycosylation Status and Presentation Format Determines Immune Responses Induced by Keyhole Limpet Hemocyanin (KLH) (52.16)
Authors: Bi Shuguang , Baum Mary , Morse Daniel 
Published: January 2023

Abstract
KLH is a heavily glycosylated protein. It can exist as 8MDa cylinders composed of 20 copies (didecamer) of a 400KDa subunit, or as separate subunits. KLH is a well-established immune stimulant, hapten carrier and generalized vaccine component. It is also used as a therapeutic vaccine against bladder cancer. Besides its application in schistosomiasis diagnosis, chronic stress such as post-traumatic stress disorder (PTSD) recently has been found to suppress KLH-induced adaptive immune responses, suggesting the potential for KLH in PTSD diagnosis. However, literature reports cite dramatically different immune responses to different preparations of the molecule, thus limiting the predictive outcome of using KLH as antigen carrier, vaccine adjuvant, vaccine or diagnostic agent. Mechanisms responsible for this variation remain largely unknown. Using lectin array and dendritic cell (DC) maturation assay, we found that KLH didecamers and subunits from different sources exhibit different carbohydrate profiles, and that the potency of KLH-induction of DC maturation varied with glycosylation status. We also found that conjugating KLH to poly (ethylene glycol)-based dendrimers significantly boosted DC maturation. Using endocytosis inhibitors, glycosylation status and presentation format was found to determine KLH uptake pathways in DCs. We thus propose that KLH can be tailored by manipulating glycosylation status and presentation format for optimal activity to meet different needs.
Ii- tumor cells present novel MHC II peptides that are tumor specific and immunogenic (52.18)
Authors: Chornoguz Olesya , Gapeev Alexei , O'Neill Michael , Ostrand-Rosenberg Suzanne 
Published: January 2023

Abstract
We have generated tumor cell-based vaccines to activate patients’ CD4+ T-cells to facilitate tumor immunity. The vaccines are based on the hypothesis that invariant chain negative (Ii-), MHC II+ , CD80+ human breast cancer cells (MCF10) present novel MHC II peptides and circumvent patients’ tolerance to their cancer. We sequenced MHC II peptides from Ii- (MCF10/DR7/CD80 and MCF10/CIITA/CD80/Ii siRNA) and Ii+ (MCF10/DR7/CD80/Ii and MCF10/CIITA/CD80) cells using LC-MS/MS. 64/116 peptides identified were unique to MCF10/DR7/CD80 and 176/228 peptides were unique to MCF10/DR7/CD80/Ii cells. 102/108 and 22/28 peptides were uniquely identified for MCF10/CIITA/CD80 and MCF10/CIITA/CD80/Ii siRNA cells, respectively. Therefore, the absence of Ii enables the presentation of unique peptides that are not presented by Ii+ or professional antigen presenting cells. Five peptides unique to Ii- and 2 peptides shared by Ii- and Ii+ cells and with the highest MHC II binding affinity, as predicted by artificial neural net analysis, were tested for their ability to activate T-cells from the blood of healthy donors or breast cancer patients. All peptides expanded tumor-reactive T-cells and induced IFNγ production. This is the first study to compare the human MHC II peptide repertoire in the absence or presence of Ii and to identify novel immunogenic MHC II-restricted peptides that are potential therapeutic reagents for cancer patients.
Acute intrahepatic CD8 T cell activation by plasmid DNA induces defective CD8 T cell immune response. (52.3)
Authors: Obeng-Adjei Nyamekye , Choo Daniel , Weiner David 
Published: January 2023

Abstract
The fate of CD8 T cells primed in the liver has been a subject of controversy in the attempt to explain the failure of immunity in chronic liver infections such as HBV, HCV and malaria. While most models show activation of CD8 T cells when liver resident cells present antigen, there are differences in opinion as to what becomes of these T cells after their initial priming. In this study, we used hydrodynamic injection that mimics acute HBV/HCV infection to express antigen in the liver, while taking advantage of the well-established LCMV P14 system, to induce acute intrahepatic T cells activation. We observed comparable CD8 T cells proliferation, up-regulation of CD44 and CD25, down-regulation of L-selectin, to the control (activation in lymphoid tissues). However, CD8 T cells primed in the liver expressed higher levels of pro-apoptotic markers such as Bim and active caspase 3, resulting in the loss of activated cells in all tissues. These liver activated CD8 T cells were incapable of protecting mice from lethal intracranial LCMV challenge. Our results confirm the up-regulation of ‘death markers’ during CD8 T cell priming in the liver, which leads to deletion of activated CD8 T cells needed to control viral infections in the liver. Thus, the failure of T cells to control chronic HBV/HCV is more likely due to defective liver priming of antigen-specific T cells.
Targeting Her-2/neu breast cancers with a plant derived natural compound, Withaferin A (53.15)
Authors: Smith Annalise , Marin Susana , Andreansky Samita 
Published: January 2023

Abstract
Over expression of oncogenic Her-2/neu protein in breast cancer cells correlates with poor prognosis and patients initially responsive to Her-2/neu targeted treatments often experience recurrence within a year of treatment. Thus, new strategies to combat these cancers should be explored. Our research focuses on the development of Withaferin A (WA), a steroidal lactone derived from the Indian ayurvedic medicinal plant Withania somnifera as an immunotherapeutic agent. The benefit of using natural plant derived products is their low toxicity, multimodal action and potential ability to enhance the immune system. Our goal is to establish WA as a chemoimmunotherapeutic agent in the treatment of Her-2/neu breast cancers. We provide evidence that WA is effective in vitro against both human and murine Her-2/neu breast cancer cells. WA induces cell death by apoptosis and increases expression of immunogenic stress proteins. Furthermore, WA up-regulated costimualtory molecules, cytokine production and antigen presentation in cultured bone marrow derived murine dendritic cells (BMDC). Additionally, in vivo administration of WA in a therapeutic setting significantly delayed tumor growth with a 10% survival benefit. Our long-term goal is to elucidate the anti-tumor immunomodulatory mechanisms of WA. Such agents that can deliver multimodal action towards cancer at both a chemotherapeutic and immunotherapeutic level might prove to be the best alternative to current treatment strategies.
APC Migration and antigen uptake is increased by the TLR2 ligand Neisserial Porin PorB (53.4)
Authors: Platt Andrew , Liu Xiuping , Berg Gretchen , Wetzler Lee 
Published: January 2023

Abstract
TLR ligands play an essential role in identifying threats to the innate immune system, which can then activate the adaptive arm. Our lab has worked with the N. meningitidis outer membrane protein Porin B (PorB), a TLR2 ligand, and shown that it increases the adaptive immune response as measured by antibody production and T cell activity. In examining the adjuvant activity of PorB we now investigate the ability of PorB to increase APC antigen uptake and migration to effector draining lymph nodes. Using an in vitro model with a fluor-linked antigen we show that PorB increases the quantity of the model antigen ovalbumin taken up by the APC in a rate dependent manner. We are in the process of characterizing the intracellular compartmentalization of the processed antigen by fluorescent microscopy of BMDM. In vivo experiments were conducted using a hock injection model and tracking the movement of the antigen through its fluorescent tag. Draining lymph nodes were examined through flow cytometry and immunofluorescence of frozen node sections. Using the latter technique, we are studying changes to lymph node morphology with the inclusion of the TLR ligand. Confirming the in vitro results, the addition of PorB to a vaccine injection increases the degree of APC migration to draining lymph nodes and the carriage of the antigen by these cells. With these results we have identified characteristics of the TLR2 ligand PorB that may account for some of its efficacy as a vaccine adjuvant.
Cross-talk between NF-kB and Neuronal Nuclei (NeuN) in HT 22 mouse hippocampus neuron: a mechanism for neuronal survival versus damage reaction (54.19)
Authors: Dasgupta Subhajit , Bandyopadhyay Mausumi 
Published: January 2023

Abstract
The Neuronal Nuclei or NeuN is well known as a marker for post mitotic neuron cell body in central nervous system of fetal as well as adult brain. However, functional role of NeuN has not been well elucidated yet. The present study demonstrated a co-association between NF-kB and NeuN in HT22 mouse hippocampus neuron cell. We found that, intracellular TLR7/8 ligand imidazoquinoline compound induced NF-kB activation in HT22 cells. The nuclear extracts of HT22 cells were found to demonstrate NeuN as well as NF-kB. Further, co-immunoprecipitation of NeuN from nuclear extracts of imidazoquinoline treated HT 22 hippocampus cells demonstrated an association with NF-kB. The observations suggested an interaction between NeuN and NF-kB in HT22 hippocampus neuron. A study has been initiated to determine a regulatory role of NeuN in management of neuronal dysfunction during dementia and epileptic seizures. Acknowledgement. The HT22 cells were provided by Dr Mark S Kindy (MUSC). We are thankful to Eileen McFadden for her support.
Anti-inflammatory activity of Tribulus terrestris in RAW264.7 Cells (54.2)
Authors: Oh Joa Sub , Baik Seung Ho , Ahn Eun-Kyung , Jeong Wonsik , Hong Seong Su 
Published: January 2023

Abstract
Inflammation is involved in various diseases, including chronic inflammatory disease and arthritis. The inflammation induced by the production of cyclooxygenease (COX)-2 and inducible nitric oxide synthase (iNOS), which are important mediators of inflammation. In this study, we investigated the ethanol extract of Tribulus terrestris (ETT) inhibited expression of COX-2 and iNOS in lipopolysaccharide(LPS)- stimulated RAW264.7 cells. We observed that ETT significantly decreased release of NO production in a dose-dependent manner in LPS-stimulated RAW264.7 cells. ETT also suppressed expression of proinflammtory cytokines, such as TNF-α and IL-4 in macrophage cell line. Our findings suggest that ETT inhibits expression of mediators related to inflammation and expression of inflammatory cytokines, which has a beneficial effect on various inflammatory diseases.