bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotine affects antigen-specific immune responses both in vitro and in vivo (B211)
Authors: Nouri-Shirazi Mahyar , Guinet Elisabeth , Zeng Menghua 
Published: January 2023

Abstract
There is increasing evidence that nicotine, an immunomodulatory component of cigarette smoke, affects immune surveillance and increases the progression of diseases. We recently reported on the effects of nicotine on human dendritic cells (DCs) and proposed a possible mechanism that links cigarette smoke to higher incidences of respiratory tract infection and asthma. To establish the causal relationship between nicotine-induced DC alterations and immunomodulation in vivo, we examined the effects of nicotine on 1) the Th-promoting capacity of mouse bone marrow DCs (BMDC), and 2) the development of cellular and humoral immune responses to antigen challenge in vivo. We report that nicotine promotes the development of mouse BMDC precursors into DCs that preferentially support the proliferation and differentiation of ovalbumin (OVA)-specific naïve T cells into effector memory cells that produce less IFN-γ and more IL-4. Further analysis revealed that these DCs indeed have a reduced capacity for antigen uptake, produce less Th1-promoting cytokine, IL-12, and display enhanced expression of Jagged, a Notch family ligand associated with producing Th2-type cells. Of particular interest, we found that injection of soluble OVA plus LPS induces clonal expansion of adoptively transferred OVA-specific CD4+ T cells in both immunized control and nicotine-exposed mice. However, the frequency of IFN-γ secreting T cells within OVA-specific expanded T cells as well as serum anti-OVA IgG2a were reduced in nicotine-exposed mice. Our in vitro and in vivo data suggests that nicotine weakens host immune defense mechanisms by affecting the development of DC-dependent Th1 cells. Philip Morris USA Inc. and Philip Morris International.
Ropporin is a novel cancer testis antigen for multiple myeloma (B212)
Authors: Chiriva Maurizio , Ferrari Raffaele , Yu Yuefei , Kelly Aaron , D’Cunha Nicholas , Cobos Everardo 
Published: January 2023

Abstract
Multiple myeloma is a fatal hematological malignancy. Despite the recent improvements in standard treatments, immunotherapy promises to be more effective due to its major specificity and its less co-related side effects. Immunotherapy’s success depends on the discovery of novel tumor associated antigens. Ropporin is a testis-specific protein, localized in the principal and end piece of sperm flagella. Our aim was to evaluate its presence in a human normal tissue panel and in a pool of multiple myeloma patients. No expression was detectable in the normal tissues, while positive band signals were seen in 52.6% of patients after PCR, and in 47.3% of patients after immunocytochemistry. We established for the first time that Ropporin is expressed at the transcriptional and at protein level in multiple myeloma. Our data strongly suggest that Ropporin is a novel cancer testis antigen and, possibly, a suitable immunological target in multiple myeloma.
Contribution of heavy-chain and conventional IgGs to the alpaca immune system during fetal, neonatal, and adult life (B215)
Authors: Daley Lisa Patryce , Purdy Stephen R , Davis William C , Appleton Judith A 
Published: January 2023

Abstract
Besides conventional immunoglobulins, camelids produce antibodies that do not incorporate light chains into their structures. Because of their considerable potential for biotechnological and therapeutic applications, these so-called heavy-chain (HC) antibodies have incited great interest in the biomedical community. Comparatively little is known about their immunological functions or the B cells that produce them. Using alpacas, we set out to clarify the life histories of the B cells that synthesize HC or conventional IgGs, and determine the contribution of these isotypes to maternal immunity that is conferred on neonates via colostrum. While conducting these studies, we confirmed the presence of a second conventional IgG isotype and showed that it is synthesized by cells that localize to the marginal zones of the spleen in adult alpacas. Also, we documented for the first time a third HC isotype, most closely related to the previously defined IgG3. Cells staining positive for this HC isotype were detected in ileal Peyer’s patches; conversely, none of the other four HC isotypes were detected at this site. In aggregate, HC isotypes comprised 38% of serum IgG in adult alpacas. All five isotypes were present in colostrum and were passively transferred to crias. The faster decline in concentrations of HC isotypes in cria blood suggests that they have a shorter half-life than the conventional IgGs.
Toll Like Receptor (TLR)- 3 mediated chemokine release in human submandibular gland cell line (B218)
Authors: Li Jingchao , Bae Ge-Hyun , Choi Se-Young , Lee Sung Joong , Oh Seog Bae , Kim Joong-Soo , Park Kyungpyo 
Published: January 2023

Abstract
The recent epidemiologic studies suggest that viral infection can be one of causative factors to induce an exocrinopathy. However, the event leading to the initiation of the disease in relation with viral infection is still unknown. In this experiment, we examined whether TLR3 is expressed in human submandibular gland (HSG) cell lines and involve in chemokine release using real-time PCR, ELISA and chemotaxis experiments. We found TLR3 mRNA was expressed in this cell line. TLR3 stimulation with poly (I: C) increased mRNA expression levels of IP-10, I-TAC, and RANTES in a concentration-dependent manner. Application of neutralization antibody of TLR3 inhibited the increase of mRNA levels, suggesting it’s specifically mediated by TLR3. We confirmed the increase of chemokine concentrations in extracellular medium of HSG treated by poly (I: C). In the chemotaxis experiment, the under layer of culture media including released chemokines from poly (I: C) treated HSG cells induced T-lymphocyte migration from the upper layer of boyden chamber. Our results suggest that TLR3 functionally expressed in salivary glands and plays a role in the initiation of inflammation.
Generation and use of monoclonal antibodies as leucocyte-markers to study the immune function in teleost fish (B219)
Authors: Jose Meseguer , Angeles Esteban M , Alberto Cuesta 
Published: January 2023

Abstract
Fish possess the first full immune system in the vertebrate evolution. To date, leucocyte abundance, distribution and function has attempted to elucidate how similar or different are the fish and mammalian immune system. Fish possess lymphocytes, monocyte-macrophages and granulocytes with main differences in the tissue origin, distribution and functioning. Lack of proper molecular markers, such as commercial specific antibodies, for fish leucocytes is still hampering the success in this field. Considering this, we immunized mice with gilthead seabream (Sparus aurata L.) leucocytes and generated monoclonal antibodies following standard protocols. We chose 3 clones (H4, D2 and C1) and characterised their specificity for seabream leucocytes by means of flow cytometry, immunocytochemistry, magnetic-activated cell sorting (MACS) and gene expression by RT-PCR. Functional studies with the isolated leucocyte populations were also conducted to ascertain their implication in phagocytosis, cell-mediated cytotoxicity or oxygen-free radical production. Generation of monoclonal antibodies is a promising field in order to get good markers for further characterisation of the fish immune system.
Work partially funded by European (QLK2-CT-2002-00722), national (AGL2005-07454-C02-01) and regional (02958/PI/05) projects.
Self antigens are partial agonists for NKT cells (B221)
Authors: Wang Xiaohua , Besra Gurdyal S , Gumperz Jenny E 
Published: January 2023

Abstract
NKT cells are regulatory T cells that recognize glycolipid antigens presented by CD1d. The antigens recognized by NKT cells include self and foreign lipids, but it is unclear whether these elicit different functional responses. Here we show that presentation of self antigens to human NKT cell clones stimulates quantitatively and qualitatively different responses than the potent exogenous antigen α-GalCer. Self antigen recognition only efficiently activated secretion of GM-CSF and IL-13, whereas α-GalCer stimulated full cytokine production (GM-CSF, IL-13, IL-4, IFNγ, and IL-2) as well as cytotoxicity and proliferation. Recognition of self antigens resulted in TCR down-regulation, CD69 up-regulation, and ERK phosphorylation, indicating that TCR-mediated signaling had occurred. However, no NKT cell Ca++ flux was detected in response to self antigen, although α-GalCer stimulated robust Ca++ signaling. Recognition of self antigens in the presence of ionomycin, which artificially induces Ca++ flux, resulted in full functional responses, including production of IL-2 and proliferation. Conversely, stimulation by α-GalCer in the presence of cyclosporin A to block calcium signaling, preferentially inhibited IL-2 secretion. Hence, NKT cell recognition of self antigens is associated with a defect in calcium signaling, and results in a partial activation phenotype.
Tetramer staining of Anaplasma marginale specific CD4 T cells following major surface protein immunization reveals the rapid loss of specific T cells in response to infection (B23)
Authors: Brown Wendy C , Han Sushan , Mwangi Waithaka , Palmer Guy H , Norimine Junzo 
Published: January 2023

Abstract
Immunization with A. marginale major surface protein (MSP)2 and Th1 adjuvants induced strong CD4 T cell proliferative and IFN-γ responses in cattle, that upon challenge were rapidly and permanently lost. To determine if A. marginale infection induced suppression or peripheral deletion of antigen-specific T cells, MHC class II tetramers were used to enumerate epitope-specific T cells following immunization of calves with a DNA construct encoding the 30-mer F2-5 epitope of MSP1a and infection six months later. As observed for MSP2, the MSP1a F2-5 peptide-specific CD4 T cell responses, still strong at the time of challenge, rapidly disappeared by 2–4 weeks. BoLA MHC class II DRB3 *1101 tetramers were constructed with the 15-mer core F2-5 epitope, designated F2-5B, linked to the DRB3 chain. Tetramer-stained PBMC obtained following immunization and challenge were selected with anti-PE beads prior to FACS analysis to increase the sensitivity of detection. The loss of MSP1a peptide F2-5-specific T cell responses was paralleled by a rapid decline in circulating DRB3 *1101-F2-5B tetramer-positive CD4 T cells after challenge, showing that the lack of response is not simply due to anergy or suppression. Our data support the hypothesis that the antigen-specific cells undergo activation-induced cell death in response to the infection, as tetramer-positive cells were not detected in spleen or liver.
CD4+CD25+ regulatory T cells attenuate hypersensitivity pneumonitis by suppressing IFN-γ secreting T cells (B25)
Authors: Park Yuna , Chung Doohyun 
Published: January 2023

Abstract
Hypersensitivity pneumonitis(HP) is developed after repeated inhalation of finely dispersed antigens. The pathogenesis of HP is complex and not completely understood. Currently, HP is mainly caused by Th1 immune response. CD4+CD25+ T cells play critical roles in preventing the development of various immune diseases. Therefore, we postulated that CD4+CD25+ T cells might contribute to attenuating HP.
To address this postulation, we investigated functional roles of CD4+CD25+ T cells in Saccharopolyspora rectivirgula (SR)-induced HP. CD4+CD25+ T cells infiltrated the lung tissue in B6 mice during the development of SR-induced HP. In CD4+CD25+ T cell-depleted B6 mice using PC61 mAb, HP was worse in terms of total cell number, SR-specific IgG in serum and bronchoalveolar lavage fluid (BALF) and SR-specific T cell proliferation than those in control B6 mice. The adoptive transfer of CD4+CD25+ T cells attenuated SR-induced HP in mice depleted CD4+CD25+ T cell. CD4+CD25+ T cell depleted mice showed elevated IFN-γ production and reduced IL-4 production in the lung during HP. Moreover, CD4+CD25+ T cell suppressed IFN-γ-producing CD4+ and CD8+ T cells in BALF with direct contact manner rather than indirect mechanism.
Taken together, these results suggest that CD4+CD25+ regulatory T cell play a protective role in SR-induced HP by suppressing IFN-γ-producing CD4+ and CD8+ T cell, which induced Th1 phenotype during the pathogenesis of HP. The enhancement of CD4+CD25+ regulatory T cell function may be useful therapeutic modality for HP.
Impaired T cell function and CD8 memory maintenance in a novel IL-7Rα knock-in mouse (B30)
Authors: Abraham Ninan , Dhanji Salim , Priatel John J , Miners M Jill , Teh Hung-Sia , Osborne Lisa C 
Published: January 2023

Abstract
Interleukin (IL)-7 is an essential growth factor for thymocyte development and survival of peripheral T cells, specifically CD8+ memory T cells. Current models such as IL-7 or IL-7 receptor alpha (IL-7Rα) knock-out mice have demonstrated the necessity of IL-7 signaling in these processes, but are unable to delineate the involvement of downstream pathways. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα449F). Thymocytes from these mice overcome a double negative (DN) stage developmental block that allows subsequent T cell maturation and peripheral migration. This is in stark contrast to the severe cytopenia seen in IL-7Rα−/− mice. These findings highlight the importance of IL-7Rα Y449-mediated signals during thymopoiesis, but also indicate a requirement for Y449-independent signals. Infection of IL-7Rα449F mice with the intracellular pathogen Listeria monocytogenes revealed that CD4 and CD8 T cells had different requirements for IL-7Rα signals. Strikingly, CD4 T cells failed to mount a detectable primary response to Listeria. Despite normal CD8 primary responses, maintenance of Listeria-specific CD8 memory was impaired in IL-7Rα449F mice. Furthermore, we show that Bcl-2 is IL-7Rα Y449-independent and insufficient for IL-7-mediated maintenance of CD8 memory.
Research funded by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research
The effect of BLyS neutralization on primary B cell compartments and responses (B31)
Authors: Scholz Jean L. , Crowley Jenni E. , O’Neill Patrick J. , Cho Yun Hee , Ward Chris , Migone Thi-Sau , Cancro Michael P. 
Published: January 2023

Abstract
B lymphocyte stimulator (BLyS) controls the proportion of transitional B cells completing differentiation and the longevity of most primary B cells. These key roles in B cell selection, survival and homeostasis make BLyS and its receptors attractive candidates for targeted B cell therapeutics. Here we have used a neutralizing hamster anti-mouse BLyS antibody to assess how BLyS depletion influences developing and primary B cell subsets, as well as how this treatment impacts primary TD and TI immune responses. Mice treated with 10F4 show rapid and substantial reductions in the transitional, follicular, and marginal zone pools which persist for ~40 days. In contrast, the only bone marrow subset affected is the mature recirculating B cell fraction. Interestingly, splenic B1 cells, but not peritoneal B1 cells, are reduced as well. Following the recovery of serum BLyS levels, peripheral reconstitution occurs gradually, such that normal B cell numbers return by day 70–80. Mice challenged with T-dependent or T-independent antigen at day 30 post-treatment with anti-BLyS mount attenuated humoral responses compared with untreated mice. Together, our results show that BLyS neutralization ablates most primary B cells but spares B lineage progenitors; and indicate that these populations, as well as BLyS per se, may be required for unabridged primary immune responses.
Effect of human recombinant interferon alpha 2b (Viferon) in treatment of severe bacterial infections in neonates. (B32)
Authors: Soldatova Irina Gennadyevna , Volodin Nicolay N. , Malinovskaya Valentina V. , Degtyareva Marina V. , Vyzhlova Eugenia N. 
Published: January 2023

Abstract
Neonates have decreased cytotoxic mechanisms and low levels of endogenous interferon production. Aim: Clinical efficacy and mechanisms of adjunctive immunotherapy with human recombinant interferon alpha 2b (Viferon) were studied in neonates suffering from severe bacterial infections. Design. 48 neonates with bacterial pneumonia were observed in NICU. 23 infants (group 1) were treated with Viferon-1, 150,000 IU per suppositorium q8h per rectum during 7 days in addition to combined antibacterial and supportive therapy. 25 babies (group 2) received the same basic therapy plus placebo instead of Viferon in similar way. Results. Clinical course of pneumonia was more favourable in neonates treated with Viferon. The duration of central venous line usage and total parenteral nutrition were significantly less in group 1 than in group 2. Inflammatory signs in blood analyses were significantly decreased after the treatment with Viferon in comparison with placebo-group. Infants treated with Viferon had significantly higher levels of CD3+, CD4+ and CD25+-lymphocytes, higher serum levels of IFN, elevation of mitogen-induced IFN-gamma production after Viferon than infants from group 2. Conclusion. Immunotherapy with Viferon improves the clinical course of severe bacterial infections and restores the balance in immune system of infected newborn infants.
Development of PKC Theta-Specific Inhibitors to Modulate T-Cell Activation (B35)
Authors: Karim Felix , Baruch Amos , Cruz Jay Dela , Maclean Derek , Das Kanad , Harrision Stehen 
Published: January 2023

Abstract
Autoimmune diseases such as psoriasis and rheumatoid arthritis involve inappropriate activation and infiltration of T lymphocytes. Protein Kinase C Theta (PKC Theta) activation is a critical step in the integrated TCR/CD28 co-stimulatory signaling cascade leading to productive T-cell activation. Mice deficient in PKC Theta have been shown to have attenuated T-cell response and are protected from antigen-induced arthritis. Efforts to develop small molecule (ATP-competitive) inhibitors of individual PKC isozymes for therapeutic applications have been largely unsuccessful due to the lack of specificity of such compounds. KAI Pharmaceuticals has developed highly selective peptide-based inhibitors for each PKC isozyme that overcome this limitation by modulating the unique intracellular translocation of individual isozymes. KAI is actively developing PKC Theta inhibitors to treat and modify autoimmune diseases. The development and characterization of these highly selective PKC Theta inhibitors/modulators will be discussed.
Antigen-independent secondary Igκ rearrangement in B-cell development – implications for receptor editing (B39)
Authors: Liu Feifei , Cowell Lindsay G. , Heikamp Emily , Kelsoe Garnett 
Published: January 2023

Abstract
Receptor editing by secondary Vκ-to-Jκ rearrangements is thought to be driven by reactivity to self. However, the evidence supporting antigen-driven editing is open to other interpretations; analysis of Igκ excision circles from birds and mice indicates continuing V(D)J recombination in cis after both functional (F) and non-functional (nF) rearrangements. We have determined the extent and nature of secondary Vκ-to-Jκ rearrangements by analyzing their intermediate cleavage products in the 103/Bcl2 cell line and in purified compartments of developing B cells from normal, Jκ−/+, and IgH transgenic mice. In all cases, we find that the ratio of F:nF VκJκ joints replaced by secondary rearrangement is approximately 1:2, the ratio expected for rearrangement without feedback of any kind. Secondary rearrangement is initiated in small pre-B cells and in BrdU pulse-labeling studies, we detected no evidence for immature to pre-B “retrograde” differentiation. Thus, “receptor editing” occurs in B cells that do not express surface Ig. Significantly, in 3H9 IgH transgenic mice, replacement rearrangements exhibited F:nF ratios of 1:2, regardless of whether the initial rearrangements were permissive or non-permissive for autoreactivity. Our results demonstrate continuing Vκ-to-Jκ rearrangement on a single chromosome without feedback and imply that “receptor editing” is an illusion of antigen-driven selection.
The spatial-temporal interactions of CD45 with the B cell receptor and regulatory roles in intracellular signaling (B45)
Authors: Tam Anthony Waiyee , Tsourkas Philippos , Raychaudhuri Subhadip 
Published: January 2023

Abstract
Background: CD45, a membrane-bound phosphatase, has been shown to enhance and inhibit intracellular signaling in many different immune cells including B lymphocytes. However, the mechanisms of CD45 have not been fully described.
Objectives: To build a computational model for B cell signaling in order to investigate the role of CD45 in the initiation of intracellular signaling upon B cell receptor ligation with antigen and the spatial-temporal interactions with the B cell receptor and signaling protein tyrosine kinases.
Methods: Kinetic Monte Carlo stochastic simulations will be used with probabilistic rate constants mapped to experimentally measured parameters. Simulation results will be tested in vitro.
Anticipated results: It will be shown that without a binding partner, CD45 will be pushed out early in the formation of the B cell immunological synapse. For the duration that CD45 interacts with intracellular Src family kinases (SFK) in close proximity of clustered B cell receptors, there is sufficient activation of SFK to initiate the signaling cascade. It will also be shown that it is critical for CD45 to be pushed out from the immunological synapse away from BCR and the SFK so that non-phoshorylated BCR should be internalized and used for antigen capture and presentation on MHC II.
530 754-5739
Expression of type III lambda interferon genes is showing similar two-wave regulation with type I alpha/beta interferon genes (B50)
Authors: Osterlund Pamela , Pietila Taija , Kotenko Sergei , Julkunen Ilkka 
Published: January 2023

Abstract
In virus infection the replication of viral genome triggers the expression of antiviral genes, like type I interferons (IFN-alpha/beta), by transcription factors activated through both TLR-dependent and independent pathways. Recently, another class of antiviral type III interferons (IFN-lambda1-3) was identified. Here is presented a detailed characterization of the IFN-lambda1 and IFN-lambda3 gene promoters and functional characterization of virus-specific activation of transcription factors regulating these promoters. Both of these promoters have a functional interferon-stimulated response element (ISRE) and NF-kappaB binding site, although the interferon regulatory factors (IRFs)-binding ISRE was the most crucial regulatory element on these promoters. Ectopic expression of the components of the three virus-induced signaling pathways (MyD88+IRF7, Trif and RIG-I) induced the activation of IFN-lambda1 promoter, whereas the IFN-lambda3 promoter was activated to higher extent only by IRF7 alone or in combination with MyD88. Recently documented IRF3 suppressor Pin1 down-regulated all the three signaling cascades induced IFN promoter activation, but not the NF-kappaB mediated transcription. These results suggest that IFN-lambda1 gene is regulated by both IRF3 and IRF7 like IFN-beta gene, whereas IFN-lambda2/3 genes are induced mainly after IRF7-mediated positive feedback.