bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and Functional Analysis of Human IL15-induced Dendritic Cells (78.43)
Authors: Okada Starlyn L , Han Shuhong , Chang Lung-Ji 
Published: January 2023

Abstract
Dendritic cells (DCs) are vital to innate and adaptive immune responses. Human monocyte-derived DCs are commonly generated in vitro via IL4 and GM-CSF (IL4 DCs). IL15 has also been shown to induce DC differentiation (IL15 DCs). Mature IL15 DCs are reported to express Langerin cell surface markers and induce a strong CD8 T cell response; however, functional differences between these two DC subsets have yet to be fully characterized. In this study, we report significant variations between the two DC subsets in morphology as well as expression of surface and secreted molecules involved in antigen presentation, co-stimulation and innate immune functions. Despite higher expression of HLA class I, HLA-DR, CD1a, DC-SIGN, CD80, CD86 and CD83 by mature IL4 DCs, IL15 DCs induced higher NK cell proliferation and stronger antigen-specific primary and memory immune responses as determined by IFN-g secretion and CD107a degranulation of autologous lymphocytes. IL15 DCs also secreted very high levels of cytokines and chemokines such as IL6, IL8, IL15, IFN-g, TNFa, CCL1 and MCP-1. Intracellular flow cytometry analysis showed that T and NK cells stimulated with IL15 DCs exhibited increased amounts of activated STAT5 and nuclear NFkB molecules. Our results indicate that IL15 DCs may play a pivotal role in the rapid development of both innate and cognate immune responses. Supported by Vectorite Biomedica Inc. and Yongling Foundation.
B Lymphocyte-Induced Maturation Protein-1/Positive Regulatory Domain I-Binding Factor 1 regulates two amino peptidases associated with antigen processing (78.9)
Authors: Piskurich Janet F , Mayorov Vladimir I 
Published: January 2023

Abstract
A diverse repertoire of specifically-trimmed peptides is presented by the Major Histocompatibility Complex Class I (MHCI) pathway of antigen presentation for immune surveillance by CD8+ cytotoxic T cells. These peptides are generated in the cytosol, then trimmed by amino peptidases to meet the binding requirements of MHCI. Two endoplasmic reticulum amino peptidases, ERAP1 and ERAP2, perform this function in human cells. Positive Regulatory Domain I-Binding Factor 1 (PRDI-BF1) called B Lymphocyte Induced Maturation Protein-1 (BLIMP-1) in mice drives the differentiation of B lymphocytes into plasma cells. We demonstrated that PRDI-BF1/BLIMP-1 regulates the MHCII pathway of antigen presentation by repressing MHC class II transactivator (CIITA) transcription. We now show that PRDI-BF1/BLIMP-1 plays a key role in modulating the MHCI pathway. Functional promoter analyses and protein/DNA binding studies demonstrate that both full-length PRDI-BF1/BLIMP-1 and a truncated form of this transcription factor called PRDI-BF1β, expressed in myeloma cells and associated with resistance to chemotherapy in diffuse large B-cell and T-cell lymphoma, mediate repression of ERAP1 and ERAP2. Repression occurs through a site nearly identical in sequence to a site for repression of CIITA. IFN-γ or ectopic expression of IRF-1 up regulates ERAP expression even in PRDI-BF1/BLIMP-1-expressing cells. The goal of this work is to uncover pathways useful in therapeutic approaches to improve the ability of the immune system to recognize and destroy PRDI-BF1-expressing tumors.
Supported by grants from the National Cancer Institute (RO1CA102203) and MEDCEN Community Health Foundation of Central Georgia.
Immune response and clinical reaction to food proteins with high vs. low/non allergenic potential in an adjuvant-free mouse model (79.17)
Authors: Gangur Venu , Parvataneni Sitaram , Gonipeta Babu , Tempelman Rob 
Published: January 2023

Abstract
Predicting allergenic potential of novel proteins present in foods such as genetically modified foods is a major challenge facing regulatory agencies and biotech industries. Here we tested the hypothesis that the adjuvant-free mouse model that we have previously reported (Birmingham et al Int Arch Allergy Immunol 2007;144(3):203-10) will be useful to distinguish human food proteins with high vs. low/non allergenic potential. Three readouts were used for testing food allergenicity: 1) systemic specific IgE antibody response to transdermal food protein exposure; 2) clinical symptoms of systemic anaphylaxis to oral food protein challenge; and 3) drop in rectal temperature (hypothermia) to oral food protein challenge. The following food proteins were tested for allergenicity: food proteins with high allergenic potential (cashew nut, milk), food proteins with low/non allergenic potential (kidney bean, Pinto bean); and a food protein with unknown history of allergenicity (Amaranth seed protein). We found that whereas, both cashew nut and milk tested positive for all three readouts of allergenicity, Pinto bean and kidney bean although induced specific IgE antibodies, did not cause systemic anaphylaxis and hypothermia. Interestingly, Amaranth seed protein induced not only a robust IgE response but also elicited clinical symptoms of systemic anaphylaxis as well as hypothermia. These data demonstrate that: 1) further testing with additional food proteins is necessary to evaluate the predictive utility of this mouse model for allergenicity testing; and 2) further studies are needed to evaluate the relationship between circulating food specific IgE antibodies and clinical sensitization for oral food induced systemic anaphylaxis. Funding: US EPA STAR Grant#R833133
SCF and IL-25 induced Th2 associated pathophysiology in chronic cockroach antigen induced asthma (79.19)
Authors: Petersen Bryan , Dolgachev Vladislav , Lukacs Nicholas W 
Published: January 2023

Abstract
Asthma is a chronic inflammatory airway disease with a nationwide prevalence of ~6%. It is associated with goblet cell metaplasia and airway hyperreactivity (AHR). Models of allergen-induced asthma exhibit increased levels of stem cell factor (SCF) and the accumulation of myeloid derived SCF receptor (c-kit)+ cells in the airway. Anti-SCF antibody treatments into the airway attenuate Th2 cytokine responses and reduce IL-25 responsiveness in CRA challenged mice in a T cell independent manner. Additional data have identified that an IL-25R+ myeloid cell accumulates in the lung during chronic allergen responses and contributes to Th2 cytokine production. When W/Wv mice were sensitized and challenged with allergen, AHR and mucous hypersecretion responses were significantly attenuated along with overall inflammatory responses. A significant reduction in IL-25R+ myeloid cells was a prominent feature that correlated with reduced Th2 cytokine responses. Subsequent experiments will further define the responses using adoptive transfer of wildtype myeloid progenitor cells to define whether the IL-25R+ myeloid cell population is reconstituted along with Th2 cytokine responses and pathophysiology.
This work was supported by NIH grant HL59178
Microarray analysis of the gene expression profile of HMC-1 mast cells following Schizonepeta tenuifolia treatment (80.14)
Authors: Sohn Sung-Hwa , Ko Eunjung , Kim Yong , Lee Ki-Heung , Kim Yangseok , Shin Minkyu , Hong Moochang , Bae Hyunsu 
Published: January 2023

Abstract
Objective: This study was conducted to evaluate the anti-inflammation mechanism of Schizonepeta tenuifolia (ST) extract and ST purified chemicals on PMA plus A23187-induced stimulation of HMC-1 human mast cells. Methods: In the present study, the anti-inflammatory effects of ST, Rosmarinic acid (RA), Pulegone (PG), and 2¥á,3¥á,24-thrihydrooxylen-12en-28oic acid (TH) on stimulated HMC-1 cells were then evaluated by analyzing IL-6, IL-8, and TNF-¥á secretion. In addition, the effects of ST, RA, PG, and TH on gene expression profiles in stimulated HMC-1 cells were evaluated by microarray and real time RT-PCR (RTRP). Results: ST, RA, PG, and TH treated HMC-1 cells were significantly suppressed pro-infalmmatory cytokines in dose dependent manner. In addition, the results of the microarray and RTRP revealed that ST regulates several pathways, including cytokine-cytokine receptor interaction (CCRI), MAPK, and the Toll-like receptor (TLR) signaling pathways. Conclusions: ST may have potential efficacy for the treatment of inflammation disease through anti-inflammation activity that occurs via inhibition of the CCRI, MAPK, and TLR signaling pathways.
Activation of Bovine NK cells through Toll-like receptors (81.1)
Authors: Mayer Sandra V , Golde William , Estes Don Mark 
Published: January 2023

Abstract
Toll like receptors (TLRs) play a critical role in the immediate detection and control of infection in mammals and are very important for initiating a series of signaling events which result in proinflammatory gene expression. Many of these receptors are type I transmembrane proteins that belong to the interleukin-1 receptor family. There are 13 TLRs already identified in mammals, 10 in humans, 10 in bovine and 13 in mice. The TLRs main functions include secretion of type 1 interferon, proinflamatory cytokines, chemokines and expression of co-stimulatory molecules. The aim of this study was to verify intracellular perforin and gamma interferon production, granzyme, perforin transcription and extra cellular gamma interferon secretion in bovine NK cells treated with TLRs ligands such as TLR2, TLR3, TLR4, TLR5 and TLR9. The cells were sorted by magnetic cell sorting with the NKp46 antibody and 24 hours later they were stimulated for 72 hours with the TLR ligands mentioned above. Our preliminary results demonstrated that flagellin (6/6) and PPD (5/6) are the most inducers of intracellular interferon gamma production followed by LPS (4/6) and CpG (4/6). When we analyzed the intracellular perforin production we verified an increase in the cells treated with CpG (4/6) or LPS (3/6). These results suggest that bovine NK cells might be activated by these TLRs ligants, otherwise further studies are needed to elucidate this hypothesis.
Keywords: Toll like receptors, bovine, NK cells.
Role of CD16 and 2B4 in activation of cytolytic and cytokine release by bovine NK cells (81.2)
Authors: Mayer Sandra V , Golde William , Scherer Charles FC , Endsley Mark , Estes Don Mark 
Published: January 2023

Abstract
Natural Killer cells (NK) are important in both antiviral, bacterial and tumor defense and constitute a major effector population of the innate immune defense. Activation of NK cells by specific cell surface expressed proteins in infected or tumor cells can induce the production of IFNg and cytotoxicity through release of cytotoxic granules such as perforin and granulysin. Bovine NK cells were recently phenotypically characterized but selective activation via cell surface receptors is not fully understood. Treatments using either inhibitory or stimulatory receptors that activate NKs can be used as a target for vaccine formulation against important bovine and human pathogens. In the present study we used lymph node-derived bovine NK cells that were activated with different conditions including activation via CD244 AND CD16 resulting in increasing IFNg and Perforin. Our studies demonstrate that specific in vitro activation conditions of purified bovine NK cells results in a rapid response via secretion of IFNg and cytotoxic granules. Insight into selective NK functional activities can be used in the development of better vaccines against rapidly replicating pathogens such as foot and mouth disease virus.
keywords: NK cells, Bovine, CD16 Receptor, CD244 Receptor
Changes in levels of Sema4A mRNA in developing thymocyte subsets in C57 mice (81.5)
Authors: Chatterjea Devavani , Linder Grace , Matthes David 
Published: January 2023

Abstract
Since their discovery in 1993, the semaphorin family has expanded to include over twenty different types of the proteins with known guidance and developmental roles ranging from heart morphogenesis and vertebrate growth to immuno-regulation. These functions of semaphorins as adaptors of peripheral immune responses in vertebrates have led us to ask whether these molecules may be important for developing T cells in the mouse thymus. We previously showed by RT-PCR that Sema4A mRNA is expressed in the thymus of 4 wk-old C57BL/6 mice. Our immuno-histochemistry studies showed that Sema4A protein is expressed in the thymus of these mice and appears localized to the medullary region. Our current findings show that by quantitative real time PCR analysis, CD4-CD8- (DN) cells as well as CD4+ and CD8+ (SP ) cells express Sema4A mRNA at 2-2.5 fold higher levels compared to CD4+CD8+ (DP) cells in the thymus of C57BL/6 mice. Taken together, our results show that levels of Sema4A mRNA fluctuate during the staged development of thymocytes. In particular, the expression pattern on DN and SP but not DP cells suggests that Sema4A may be used as an adaptor molecule in the expansion of DP cells during positive selection and naïve SP cells once again express Sema4A mRNA prior to their exit from the thymus upon which this molecule serves its known accessory role in antigen-mediated peripheral activation and maturation.
Post-thymic T cells undergo maturation in secondary lymphoid organs (82.11)
Authors: Houston Evan , Fink Pamela 
Published: January 2023

Abstract
T cell development was traditionally thought to occur in its entirety in the thymus, giving rise to fully developed naïve T cells ready to patrol the lymphoid periphery. However, characterization of T cells that have recently left the thymus was hampered by their lack of a unique cell surface marker. With the aid of new murine model in which those recent thymic emigrants (RTEs) are specifically labeled, RTEs been shown to undergo further changes in the lymphoid periphery prior to gaining full immunocompetence. With this model, our lab has demonstrated that RTEs are functionally dampened and phenotypically immature relative to the rest of the mature naïve T cell pool.
To aid in understanding the significance of this continued peripheral maturation, the mechanism driving this process is under investigation. We have found that exit from the thymus is required for full RTE maturation, and that this maturation process occurs progressively. We have also found that RTE maturation takes place within secondary lymphoid organs. In secondary lymphoid organs, IL-7 and MHC, homeostatic factors for naïve T cells, are dispensable for maturation, while dendritic cells do influence the maturation process. This work suggests that the process of RTE maturation is a dynamic process that is actively regulated by factors contained within the lymphoid periphery.
This research was supported by grants from the Cancer Research Institute and the National Institutes of Health.
Homeostasis of CD4+ memory and regulatory T cells occurs independently of NF-¿B (82.12)
Authors: Cornish Georgina , Ley Steve , Seddon Benedict 
Published: January 2023

Abstract
Deletion of I kappa B kinase (IKK2) under the control of cre-recombinant drivers lck-Cre and CD4-Cre, both expressed before thymic selection, interferes with normal naïve T cell activation and consequently mice fail to generate regulatory and memory CD4 T cells. However, it is not known whether the requirement for IKK2 expression extends beyond the initial inductive events required for generation of these populations. With this premise, the current study asks whether IKK2 signals are necessary for survival and/or maintenance of Treg and CD4 memory. We achieved this by specifically deleting IKK2 in mature peripheral T cells using an OX40cre driver, specifically deleting NF-κB signalling in regulatory and memory T cells post activation. Surprisingly, we find that IKK2 signalling is dispensable for normal homeostatic maintenance of both memory and regulatory T cells as mice with OX40 regulated deletion of IKK2 have normal numbers of Treg and CD4 memory. However, studies are ongoing to elucidate the mechanism by which of IKK2 mediates memory and regulatory T cell survival.
Toso expression during B cell development (82.3)
Authors: Choi Seung-Chul , Narayanan Sriram , Borrego Francisco , Coligan John E 
Published: January 2023

Abstract
Regulated apoptosis is essential for both the development and homeostasis of the immune system. Fas-mediated cell death has been implicated in apoptosis during the development and homeostasis of lymphocytes, and this apoptosis pathway is regulated by the interplay of BCL-2-family members, as well as other factors, such as cytokine withdrawal. However, Toso (also known as Fas Apoptosis Inhibitory Molecule-3) expression has been reported to inhibit Fas-mediated cell death. We isolated immune cells from the spleen and found that B cells expressed high levels of Toso mRNA compared to T cells, NK cells, granulocytes, macrophages and monocytes. After stimulation by LPS, anti-CD40 or anti-IgM, Toso expression is dramatically down-regulated in splenic B cells. Further analysis showed that bone marrow B cells express lower levels of Toso mRNA than splenic B cells. We sorted the bone marrow B cells into development stages and found that only immature B cells expressed high levels of Toso mRNA compared with pro-, pre- and mature B cells. We hypothesize that Toso has a role in normal B cell development and maintenance. To examine this, we are using Toso knockout and transgenic mice.
This work was supported by the NIAID intramural research program.
A role for CMV infection in expansion of dysfunctional IL-7 receptor alpha low memory CD8+ T cell with aging. (83.11)
Authors: Lee Won-Woo , Kang Seong-Wook , Lee Seung-Hyun , Shah Kamini , Kang Insoo 
Published: January 2023

Abstract
We recently reported an age-associated expansion of human memory CD8+ T cells expressing low levels of IL-7 receptor alpha chain (IL-7Rα) that is crucial for cell survival. These cells have limited T cell receptor (TCR) repertoire and impaired TCR-mediated proliferation. Chronic persistent viral infection is suggested as a factor that expands memory CD8+ T cells with aging and suppresses their function. Thus, we explored the role for cytomegalovirus (CMV) infection in expanding IL-7Rαlow memory CD8+ T cells and suppressing their TCR function via leukocyte Ig-like receptor-1 (LIR-1) with inhibitory function. CMV-infected donors have a higher frequency of IL-7Rαlow memory CD8+ T cells than CMV-uninfected donors in the elderly but not in the young. Most expanded IL-7Rαlow cells express LIR-1 and such expression correlates with replicative senescent marker CD57. The frequency of IL-7Rαlow memory CD8+ T cells is also higher in CMV-uninfected elderly donors than in CMV-infected and -uninfected young donors, suggesting that a factor(s) additional to CMV infection exists for expanding these cells. The expression of IL-2/15 receptor beta chain (IL-2/15Rβ) on IL-7Rαlow memory CD8+ T cells is higher in the elderly than in the young, suggesting IL-15-mediated expansion of them. Our data suggest that age-associated expansion of IL-7Rαlow memory CD8+ T cells is driven by both CMV infection and IL-15.
Basophils induce CD8 T cell IL-10 production (83.14)
Authors: Min Booki , Kim Sohee , Shen Tao 
Published: January 2023

Abstract
There is increasing evidence suggesting that basophils play a crucial role in developing Th2 type immunity. We previously reported that basophils cocultured with naive CD4 T cells stimulated with antigen promote differentiation of the T cells into IL-4-producing cells. In the present study, we examined whether basophils alter CD8 T cell differentiation pathway. Stimulation of OVA-specific OT-I CD8 T cells with peptide pulsed splenic DCs primarily induced T cell production of IFNγ. Addition of basophils into the coculture significantly inhibited IFNγ production. Unlike CD4 T cells, CD8 T cells cocultured with basophils did not produce IL-4. Instead, CD8 T cells activated in the presence of basophils produced significant levels of IL-10. The IL-10 production was greatly diminished when anti-IL-4 Ab or IL-4KO basophils were used in the culture, indicating that IL-4 is necessary for programming CD8 T cell IL-10 production. However, adding rIL-4 into CD8/DC coculture was not sufficient to induce IL-10 production. CD28-mediated costimulation dramatically enhanced T cell IL-10 production, yet neither ICOS nor CD86 was involved in IL-10 production. Finally, CD8 T cells producing IL-10 did not display regulatory cell phenotypes. Collectively, these results suggest a novel immunomodulatory function of basophils that efficiently induce CD8 T cell IL-10 production via IL-4-dependent and -independent mechanism.
The absence of Aire does not alter the CD8 T cell repertoire to infection (83.5)
Authors: Davenport Miles P , Valkenburg Sophie , Guillonneau Carole , Hubert Francois-Xavier , Cukalac Tania , Curtis Joan M , Stambas John , Scott Hamish , Venturi Vanessa , Kedzierski Lukasz , Kedzierska Katherine 
Published: January 2023

Abstract
Expression of the Aire molecule is thought to be important for self-tolerance through promoting ectopic expression of tissue-specific antigens in the thymus. In the absence of Aire, animals develop a variety of autoimmune conditions. It is unclear whether the absence of self-peptides in the thymus effects the selection of all T cells in the thymus (because they see a different mix of self-peptides), or only allows through a few self-specific cells, without perturbing selection of other cells. Here we study the CD8+ T cell responses to two well characterized influenza virus epitopes (DbNP366 and DbPA224) in AIRE +/+ and AIRE -/- mice using single cell sequencing of T cell receptors (TCR). Studying a total of approximately 1500 TCR Vbeta sequences from 25 mice, we find no differences between the responses in the presence or absence of Aire. This suggests that the absence of Aire does not perturb selection of the majority of T cells, but instead opens a small window allowing survival of a few self-specific cells.
Brief costimulation through ICAM-1 of human naïve CD4+ T cells induces differentiation to a memory phenotype days later (83.9)
Authors: Dotson Abby L. , Kohlmeier Jacob E. , Cool Kelli M. , Benedict Stephen H. 
Published: January 2023

Abstract
We previously demonstrated that costimulation through ICAM-1 induces differentiation of human naïve CD4+ T cells to a memory phenotype. Similar to results of costimulation through CD28, the phenotype includes expression of a cell surface protein array characteristic of T memory and a robust proliferative and cytokine response to low-level stimulation through the TCR complex alone. In the present work we describe the kinetics of differentiation in response to costimulation through ICAM-1 as compared with CD28 and define the minimal time that costimulatory signals are required for the naive T cells to achieve the memory phenotype. In addition, costimulation through ICAM-1 induces T cells with distinct homing properties.
This work was supported by the National Institute on Aging/NIH.