bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+TH2, not TH17 cells mount antigen specific recall response and drive allergic inflammation (P6029)
Authors: Liu Bo , Chen Chun-Yu , Lee Jeeboong , Burwinskel Karen , Wang Yui-Hsi 
Published: January 2023

Abstract
Allergic asthma is a heterogeneous inflammatory disease of the airway. In addition to CD4+ TH2 and TH17 cells of the adaptive immunity, recently described innate lymphoid cells (ILC2) also contribute to the pathogenesis of allergic asthma. However, it remains unclear that which cell type is responsible for mounting antigen-driven immune response at the recall phase of allergic inflammation. Repeated intranasal OVA re-challenges induced a significant expansion of TH2, not TH17 or ILC2 cells in rested mice that were previously sensitized with OVA plus papain. Consequently, the amount of IL-5 and IL-13, not IL-17 or IFN-γ production in the lung of mice re-exposed to OVA antigen were significantly elevated than those of mice sensitized only. Mice ablated of CD4+ T cells failed to respond to repeated OVA antigen re-challenges and exhibited ameliorated allergic airway inflammation, while their lung ILC2 remained intact. Furthermore, STAT6-deficient mice that lacked TH2 cells also failed to mount allergic recall response to OVA antigen, despite of their competency in eliciting TH17 immune response. Collectively, our results suggest that lung resident antigen specific CD4+TH2 cells, not TH17 or ILC2 cells, induced after sensitization are the primary cell type responsible for mounting allergen recall response that exacerbates allergic inflammation.
Allergic lung disease is enhanced by antigen-specific B cells (P6033)
Authors: Lindell Dennis , White Maria 
Published: January 2023

Abstract
Previous studies from our laboratory have demonstrated that B cells play an important role in the initiation and maintenance of chronic allergic lung disease (asthma), and ascribed much of this role to antigen presentation (Lindell et al. PLoSONE 2008). Although present at higher frequency than other organs, antibody secreting B cells in the lungs represent a small proportion (&lt;0.1%) of the overall B cells in the lungs. As alternative strategies to study the role of B cells in this disease, we have used novel flow cytometric techniques to detect the de novo expansion of antigen-specific B cells during allergic lung disease, as well as utilizing adoptive transfer of naive antigen-specific B cells. Mice were immunized with hen egg lysozyme and a cohort of these mice received adoptive transfers of HEL-specific B cells from MD4 mice. Our data indicate that the addition of antigen-specific B cells augmented mucus production in the lungs. Mechanistically, this was associated with increased T cell responses in the lungs (a 4-fold increase in CD69+ CD4+ and CD8+ T cells), significantly higher levels of IL-13 and IL-17a, as well as overall inflammation, although very few HEL+ B cells were found in the lungs, and we observed no increase in HEL-specific antibodies. These data suggest that B cells predominantly contribute to allergic disease by amplification of the T cell response, rather than via the production of antibodies.
Divergent roles of two neuroimmune semaphorins, Sema4A and Sema4D, in regulation of experimental asthma severity (P6041)
Authors: Chapoval Svetlana , Nkyimbeng-Takwi Eusebius-Henry , Shanks Kathleen , Smith Elizabeth , Iyer Apoorva , Lipsky Michael , DeTolla Louis , Keegan Achsah 
Published: January 2023

Abstract
Allergic asthma is characterized by exaggerated Th2 inflammation resulting from interaction between DC and T cells. Molecules acting in this interaction, regulating cell activation and differentiation are desirable therapeutic targets. Based on the previously published data and our results, we hypothesized that neuroimmune semaphorins play critical costimulatory roles in DC - T cell interaction, thereby influencing allergic lung inflammation. To test our hypothesis, we used Sema4A-/- and Sema4D-/- mice in the mouse model of OVA-induced allergic lung response. Our results have shown that both molecules play critical but opposite roles in disease severity. It was significantly potentiated by Sema4A deficiency, what included increased eosinophilic infiltration, AHR, local/systemic IL-13 levels, sera OVA-specific IgG1/ IgG2b/IgE levels, and decreased Treg numbers. Moreover, we defined that Sema4A expression on CD4+ T cells but not on DC was important for Th2 response regulation. In contrast, we found a decrease in lung inflammation and BAL Th2 cytokine levels in allergen-treated Sema4D-/- mice relative to WT mice. In addition, T cell proliferation in OVA323-339 - restimulated Sema4D-/- cell cultures was downregulated suggesting a costimulatory role of Sema4D for T cell activation. However, AHR was not affected by Sema4D deficiency suggesting its negligible role in airway physiology. These data define both molecules as important regulators of Th2-driven lung pathophysiology.
Differential regulation of IDO activity in human dendritic cells through ligation of different c-type lectins: implications for allergic sensitization (P6055)
Authors: Ghaem Maghami Amir , Salazar Lizama Fabian , Skahib Farouk 
Published: January 2023

Abstract
Indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan metabolism, plays a critical role in regulating immune responses. IDO has been shown to have a protective effect in different models of experimental allergy and asthma however its role in human allergy has remained elusive. Recent work by our group showed that Der p 1 (a major house dust mite allergen), through engaging mannose receptor (MR) on dendritic cells (DCs), could modulate IDO activity. This in turn was shown to bias immune responses towards a Th2 phenotype. Here we studied the relationship between two major ‘allergen receptors’ on DCs namely MR and DC-SIGN in regulating IDO activity in order to further define the role of these receptors in controlling allergen induced Th2 immune responses. Our data indicates that IDO expression and activity in human DCs can be differentially regulated by engagement of MR and DC-SIGN. Intriguingly, we have shown that simultaneous activation of DCs with LPS (a known inducer of IDO activity) and either MR or DC-SIGN ligands has opposing effects on IDO activity in DCs with the MR ligation causing a decrease in IDO activity whilst DC-SIGN engagement causing an increase. Such opposing effect is likely due to differential activation of a number of downstream signalling molecules. Better understanding of these pathways could shed light on a range of host-pathogen interactions involving these key receptors including those occurring in the context of allergic sensitisation.
Phenotypical characterization of Treg cells in ocular allergy patients. (P6059)
Authors: Galicia-Carreón Jorge , Palomares-Ordóñez Jose , Hong Enrique , Pérez-Tapia Sonia , Jiménez-Martínez María 
Published: January 2023

Abstract
Purpose: To evaluate frequency of T regulatory cells (Tregs) and homing receptor expression in patients with allergic conjunctivitis (AC). Methods: Peripheral blood mononuclear cells (PBMC) were isolated from healthy donors (HD) and AC-patients and labeled with mAbs against CD4, CD25, FOXP3, CCR4, CCR5, CCR7, CCR9, CD103 and CD108 before and after antigen stimulation with Dermatophagoides pteronyssinus (Der p). All cells were analyzed by flow cytometry and culture supernatants were recovered to analyze IL-10 and TGF-β. Results. AC-patients showed 55-times more CD4+ CD25+ cells than HD. Most of CD4+ CD25+ cells were FOXP3-, also these cells were CCR4+ and CCR9+ cells. After culture, no changes were detected in frequency of CD4+ CD25+ FOXP3+, nor FOXP3- T cells. Interestingly, we observed increased expression of CD103 and CD108 on T cells and IL-10 only in AC-patients. Conclusions. Circulating Tregs were decreased in allergic conjunctivitis patients, and these cells were expressing homing receptors associated to mucosa migration; after specific stimuli, these cells were able to express CD103 and CD108 on its surface; taken together these results suggest that in allergic conjunctivitis patients these cells could be migrating to conjunctival mucosa associated-lymphoid tissue remaining a phenotype related to Tr1 cells.
The leucine zipper transcription factor BATF induces IL-10 and IL-3 in allergic asthma (P6061)
Authors: Sopel Nina , Übel Caroline , Hildner Kai , Finotto Susetta 
Published: January 2023

Abstract
The transcription factor BATF is essentially involved in the differentiation of Th17 and follicular T helper cells. In B cells BATF influences the class-switch recombination of immunoglobulins. In an experimental model of allergic asthma we previously observed that BATF-/- mice do not develop asthma. We found that airway inflammation, hyperresponsiveness and eosinophilia were decreased, concomitant with lower serum IgE levels and reduced Th2 and Th17 cytokine secretion in the lung. Here we show an inhibition of IL-10 secretion in in vitro differentiated Th17 cells lacking BATF, while the expression of IRF4 mRNA was not altered. We confirmed a defect of IL-10 secretion in supernatants of total lung cells isolated from BATF-/- mice sensitized and challenged with OVA. Furthermore, IL-3, an important growth factor for the survival of eosinophils, basophils and mast cells, was also reduced in the supernatants of lung CD4+ T cells isolated from BATF-/- mice. Consistently, in BATF-/- mice treated with OVA, the number of lung mast cells expressing the IL-3 receptor α-chain was decreased. This defect was also confirmed in bone marrow derived mast cells. Taken together, BATF seems to play an important role not only in Th17 and Tfh differentiation but also in mast cell development. Therefore, local inhibition of BATF expression in the lung might be a feasible strategy for treating airway inflammation seen in allergic asthma.
Glucocorticoid induces pentraxin 3 expression through mitogen-activated protein kinase pathway in human airway smooth muscle cells (P6013)
Authors: Zhang Jingbo , Koussih Latifa , Shan Lianyu , Soussi Gounni Abdelilah 
Published: January 2023

Abstract
Long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition receptor that links innate immunity, inflammation, and matrix deposition. Glucocorticoids (GC) are an important anti-inflammatory treatment in asthma. Previous studies have demonstrated that GC had divergent effects on PTX3 production in diverse cell types. In this study, we first evaluated whether GC alone induced and, under inflammatory conditions, enhanced and extended PTX3 production in Human airway smooth muscle cells (HASMC) and investigated the plausible molecule mechanism regulating the induction of PTX3. HASMC transfected with PTX3 promoter constructs were treated with dexamethasone (Dex) or and TNF. We demonstrated Dex induced and synergized with TNF to augment PTX3 protein levels. However, Dex does not influence the mRNA levels and promoter activity of PTX3 alone, but it decreased the effect of TNF-induced PTX3 promoter activity. Further results had shown that Dex increased TNF-induced PTX3 mRNA stability. Primary HASMC pretreated with inhibitors of p42/p44 ERK, but not p38 or JNK-MAPK, significant decrease in PTX3 release on Dex- and TNF-treatment. Taken together, our data provide the first evidence of Dex-induced PTX3 expression in HASMC maybe occurred posttranscriptional mechanisms and via p42/p44-MAPK signaling pathways. Our results raise the possibility that HASMC may play a role in airway inflammation via PTX3-dependent pathway.
Interferon α/β receptor signaling plays a critical role in regulatory T cell development and function (P1093)
Authors: Metidji Amina , Punkosdy George , Shevach Ethan 
Published: January 2023

Abstract
Type I IFNs are a family of cytokines with both antiviral and immunomodulatory properties. While the antiviral effects are appreciated, the immunomodulatory properties are less clear. Given the immunomodulatory properties of Treg, we have considered a possible role for IFNα/βR signaling in Treg development/function. Treg from WT and IFNα/βR deficient (-/-) mice were equal in number and in vitro/in vivo suppressive activity. Therefore, we set up a model to test IFNα/βR-/- Treg fitness in a competitive environment using bone marrow chimeras reconstituted with a 1:1 mixture of WT and IFNα/βR-/- cells. While the WT to IFNα/βR-/- ratio of all T cells was significantly skewed toward WT in these mice, skewing was most pronounced in the Treg compartment. The disadvantage of the IFNα/βR-/- Treg in the competitive environment was likely due to a defect in development and/or survival, as the ratio of IFNα/βR-/- Treg was markedly decreased in the thymus, and peripheral IFNα/βR-/- Treg had a significantly higher frequency of active caspase positive cells. The fitness of IFNα/βR-/- Treg was further examined in a disease model by testing their capacity to rescue the scurfy disease phenotype. IFNα/βR-/- Treg in chimeric mice reconstituted with scurfy and IFNα/βR-/- bone morrow were unable to control effector T cell activation and tissue inflammation. Collectively, these data demonstrate a critical role for IFNα/βR signaling in the development and/or survival of Treg.
CCR7 coordinates paracrine interleukin-2 cross-talk between central memory and regulatory T cells and controls the homeostatic balance between regulatory T cell subsets (P1065)
Authors: Smigiel Kate , Richards Elizabeth , Thomas Kerri , Campbell Dan 
Published: January 2023

Abstract
The importance of IL-2 in immune suppression mediated by Foxp3+ Treg cells is well established. However, IL-2 is not required for Treg cell development, in vitro suppression, or to maintain total cell number; thus, the mechanism by which IL-2 controls Treg cell activity remains unclear. We demonstrate that CD44lo CD62Lhi lymphoid tissue-resident Treg cells require IL-2 for survival and maintenance, whereas CD44hi CD62Llo Treg cells with a peripheral tissue homing phenotype are IL-2 independent. We termed these subsets central (cTr) and effector Treg (eTr) cells, respectively, due to their unique homeostatic requirements and migratory potential. Furthermore, we show that the chemokine receptor CCR7 provides cTr cells access to IL-2 by coordinating their localization in proximity to IL-2-producing CCR7+ Foxp3- central memory cells in the T cell zones of secondary lymphoid tissues. Collectively, our data demonstrate that the factors governing the homeostasis and maintenance of different Treg cell subsets are highly dependent on their tissue and microenvironment localization and indicate that loss of immune tolerance in the absence of IL-2 or CCR7 is due to an imbalance of cTr and eTr cells.
Role of immunological synapse and kinapse in peripheral tolerance. (P1105)
Authors: Beuneu Helene , Dustin Michael 
Published: January 2023

Abstract
In the lymph node, T cells can receive signals through the recognition of pMHC during both long-lived (&gt;5 minutes) synapses or short-lived (&lt;5 minutes) kinapses with antigen presenting cells (APC). It has been shown that injection of low dose antigenic peptide can lead to T cell tolerance and T regulatory cells induction in vivo. Here, we are evaluating the impact of MHC-peptide potency, peptide dose and APC frequency on induction of tolerance and Treg in relation to the dynamics of T cell-antigen presenting cell (APC) interactions. We hypothesize that induction of tolerance will be a function of signal integration by T cells and that the formation of synapses will favor tolerance induction when the frequency of APC is low based on the ability of rare APC to capture T cells with MHC-peptide potency and dose supporting synapse formation. In vitro, the high potency MHC-peptide has an advantage over the low potency MHC-peptide for Treg induction when APC frequency is low. In vivo, the low potency MHC-peptide induces Treg and tolerance through kinapses. We are now in the process of characterizing, in vivo, the tolerance and Treg induction in condition where the number of APC is limited using a mixed bone marrow chimera approach.
Transient alteration in cytokine patterns following influenza vaccination detected by Ki-67 expression and automated multiparameter analysis of flow cytometry. (P4311)
Authors: Mosmann Tim , Li Xi , Zand Martin , Wu Hulin , Weaver Jason , Qi Yilin 
Published: January 2023

Abstract
We previously showed that seasonal Trivalent Inactivated Influenza Vaccine (TIV) induces a strong, transient CD4 T cell response in healthy adults, measured at days 4-6 after vaccination as influenza-specific CD4 T cells expressing Ki-67. We have now examined the phenotype of the vaccine-responsive cells, using a whole blood assay, high-dimensional flow cytometry and automated population identification by the SWIFT algorithm, which quantifies responding populations, and helps reveal unexpected population changes. A strong Ki-67+ CD4 T cell response was detected in 10/10 subjects. At day 0, Influenza-specific CD4 memory cells mostly produced Interferon gamma, Tumor Necrosis Factor alpha and Interleukin 2 in response to in vitro restimulation. After 4-6 days, the Ki-67- influenza-specific T cells expressed a similar cytokine pattern as before vaccination, whereas the Ki-67+ cells produced more Interferon gamma but much less Tumor Necrosis Factor alpha and/or IL-2. Our interpretation is that influenza-specific CD4 T cells are recruited to lymph nodes, proliferate and express Ki-67, then return to the circulation at about 4 days, still expressing Ki-67. The dominant Interferon gamma single-positive phenotype in Ki-67+ population may be a transient state of the normal multiple cytokine producers, or a transient effector population that dies, or rapidly leaves the circulation to reside in tissues.
Neonatal immunization with respiratory syncytial virus glycoprotein fragment induces protective immunity in the presence of maternal antibodies in mice (P4277)
Authors: Kim Jae-Ouk , Noh Youran , Shim Byoung-Shik , Cheon In Su , Rho Semi , Kim Heejoo , Kang Chang-Yuil , Chang Jun , Song Man Ki 
Published: January 2023

Abstract
Respiratory syncytial virus (RSV) is the major cause of severe lower respiratory tract infections in infants and the elderly worldwide. The significant morbidity and mortality associated with this infection underscores the urgent need for development of an RSV vaccine. In this study, we first show that intranasal administration of RSV glycoprotein core fragment (Gcf) to neonatal mice can induce systemic humoral immune responses and protective immunity against RSV without causing lung eosinophilia, although antibody response was shifted to a Th2 response. Next, we examined whether the presence of maternal anti-RSV antibodies affects the responsiveness and protection efficacy of Gcf in newborn mice, since infants can have RSV-specific maternal antibodies since adults are frequently reinfected with RSV. Intranasal administration of Gcf induced antibody response and IFNγ secretion and protected mice against RSV challenge without lung eosinophilia even in the presence of high levels of RSV-specific maternal antibodies. Thus, our findings suggest that Gcf may be an effective and safe RSV vaccine during the neonatal period.
A proteome-wide comparison of human antibody responses to the standard polyclonal vaccine for smallpox prevention and the monoclonal replacement ACAM2000 (P4321)
Authors: Ulrich Robert , Pugh Christine , Keasey Sarah , Pittman Phillip 
Published: January 2023

Abstract
Smallpox was eradicated in the 1980s due to the success of vaccines such as Dryvax (Wyeth Laboratories, Inc., U.S.). However, production of an improved live-virus vaccine was needed due to the limited amount of Dryvax doses available, as well as manufacturing concerns over the sterility and the clonal heterogeneity of the vaccine. Clones isolated from Dryvax produce variable numbers of antigens important for protective immunity or contributing to reactogenicity. In 2008, ACAM2000 (Acambis, Inc™), a single-plaque-purified vaccinia virus derivative of Dryvax, replaced the first-generation, polyclonal smallpox vaccine. We examined human responses to Dryvax and ACAM2000 by using a protein microarray comprised of approximately 90% of the poxvirus proteome (245 proteins) to measure protein-specific IgG in sera of 71 individuals responding to a single vaccination. We observed robust antibody responses to 21 poxvirus proteins in recipients of either product (p-value ≤0.0002), while other protein antigens could be used to distinguish vaccination with Dryvax from antibody responses to the monoclonal vaccine.
Immunosuppressive effects of early-life exposure to combustion-derived particulate matter: implications for enhanced severity due to respiratory tract infections (P3218)
Authors: Saravia Jordy , You Dahui , Lee Greg , Cormier Stephania 
Published: January 2023

Abstract
The association of elevated levels of ambient particulate matter with increased morbidity and mortality due to respiratory tract infections has been well documented. Interestingly, infants and young children appear to be the most vulnerable to these adversities. Using mice to model early-life exposure to combustion-derived particulate matter (CDPM), we demonstrate the development of an immunosuppressive environment in the lung as evidenced by increases in tolerogenic dendritic cells, regulatory T cells (Tregs), and IL-10 production and impairment of T effector proliferation in response to antigen. Specifically, infant mice co-exposed to CDPM and house dust mite allergen failed to develop certain hallmarks of asthma (e.g. airway hyperresponsiveness, eosinophilia, Th2 inflammation) while maintaining others (e.g. increased mucus production, elevated serum IgE). To investigate the effects of CDPM-induced immunosuppression on viral infections, exposed neonatal mice were infected with influenza (H1N1). CDPM-exposed and infected mice had significantly reduced pulmonary cytotoxic/helper T cell effector responses (Tc1, Tc2, Tc17/Th1, Th2; respectively) and significantly elevated Tregs compared to unexposed and infected mice. Consequently, this impairment in effector responses led to increased viral loads in the lungs of CDPM-exposed mice. Our data suggest a mechanism of exposure-mediated modulation of pulmonary disease in infants.
Distinct LLO-specific CD4 T cells infiltrate the intestinal mucosa following oral Listeria monocytogenes infection. (P3224)
Authors: Fu Han-Hsuan , Sheridan Brian , Pham Quynh-Mai , Schubert Wolf-Dieter , Freitag Nancy , Lefrançois Leo 
Published: January 2023

Abstract
Listeria monocytogenes (LM) is an enteroinvasive pathogen and the cause of listeriosis, a highly fatal foodborne infection. Using an oral LM infection model, we show that a subset of blood-borne listeriolysin O (LLO)-specific CD4 T cells transiently expressed the α4β7 integrin early after infection. Antigen-specific CD4 T cells rapidly accumulated in the mucosa and mounted a robust recall response following secondary infection. On day 9 post LM infection, LLO-specific CD4 T cells in the mucosa are almost exclusively Ly6Clow/CD27low and this population persists throughout memory. In contrast, LLO-specific CD4 T cells isolated from the spleen and MLN were heterogenous for CD27 and Ly6C expression. Mucosal LLO-specific CD27lowLy6ClowCD4 T cells produced IFN-γ and IL-2 and a small subset also produced IL-17. Interestingly, IL-17 production increased in mucosal memory CD4 T cells. Furthermore, IL-17 production was increased in mucosal CD4 T cells in CD69-deficient mice. However, mixed bone marrow chimera studies indicated that this phenomenon is independent ofCD69 expression on responding CD4 T cells. Depletion of CD4 T cells during memory led to higher bacterial burden in the gut and spleen. These results indicate that mucosal effector and memory CD4 T cells are phenotypically and functionally distinct from their splenic counterparts. Thus, our findings demonstrate an important role for mucosal memory CD4 T cells in protection against oral infection.