bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cow’s milk specific IgE and IgA as a predictor of outcome in oral immunotherapy (VAC9P.1067)
Authors: Rahman Tanvir , Lejtenyi Duncan , De Schryver Sarah , Fiter Ryan , Piccirillo Ciriaco , Ben-Shoshan Moshe , Mazer Bruce 
Published: January 2023

Abstract
Cow’s milk allergy (CMA) is defined as an immunologic adverse reaction to cow’s milk proteins. It affects 2-3% of infants, and 85% of CMA resolve spontaneously within the first 5 years of life. Those with persistent CMA have a lifelong threat of anaphylaxis. 20 patients were recruited for a trail of CM oral immunotherapy. Blood samples were collected at baseline and at multiple timepoints during a trial. Specific IgE, IgA to casein, b-lactoglobulin (BLG) and alpha-lactalbumin (ALA) were measured by Enzyme-Linked Immunosorbent Assay(ELISA). CM-specific IgE responses decreased by 5 to 10 times baseline. Importantly, in one patient there was no detectable sIgE after 6 months post OIT. As the role of specific IgA is poorly understood we measured specific IgA to the three CMA components in a subset of subjects. sIgA was increased significantly over time in 4 of 6 patients, unaltered in 1 patient, and was variable in one patient. At the end of oral immunotherapy, sIgA returned towards baseline. In summary, as patients underwent oral immunotherapy to milk, sIgA increased in parallel to the decrease in IgE in most subjects tested. CM specific IgA may help predict responses to oral immunotherapy for milk.
Immune modulation of IgE and T regulatory cells in horses vaccinated with viral vaccines. (VET1P.1117)
Authors: Behrens Nicole , Gershwin Laurel 
Published: January 2023

Abstract
West Nile virus (WNV) a neurotropic flavivirus is the leading cause of mosquito-borne encephalitis in the United States. While there is no current WNV vaccine for humans there are several vaccines for horses. These vaccines are designed to protect against this deadly virus; however, many are causing type-1 hypersensitivity IgE-mediated allergic responses that include local and severe systemic anaphylaxis. Many viral vaccines share contaminating non-target proteins that can act as antigen to elicit IgE. We compared IgE levels to those of T regulatory cell populations’ pre and post vaccination, which showed a significant inverse correlation. We hypothesize the addition of CpG oligonucleotides administered with vaccines will modulate the immune system, driving it towards protective immunity, through up-regulation of T helper 1 cells. Thirty horses were evaluated pre and 7 days post vaccination for T regulatory cell production and specific IgE. Peripheral blood mononuclear cells isolated pre and post vaccination were analyzed for expression of CD4, CD25 and intracellular Foxp3 with multicolor flow cytometry. Antigen specific IgE and cytokine supernatants were evaluated by ELISA. The addition of the CpG oligonucleotide significantly increased the production of T regulatory cells in response to antigen in-vitro and in-vivo; with this we can hope to provide a safer alternate vaccination strategy, particularly for horses that have demonstrated a pro-allergic phenotype.
Characterization of major histocompatibility complex class I genes and alleles of the California sea lion (Zalophus californianus) in relation to development of sea lion urogenital carcinoma (VET2P.1130)
Authors: Duckworth Ellen , Gulland Frances , Cohen Noah , Criscitiello Michael 
Published: January 2023

Abstract
Decades of global environmental change have impacted the overall health of many wildlife species, and emerging infectious diseases, biotoxicoses, and cancers are being increasingly recognized. California sea lions have an unusually high incidence of an aggressive, widely metastatic urogenital carcinoma that has affected 26% of the adult animals that died following stranding on the central California coast in the past decade. A gamma herpesvirus, environmental pollutants, major histocompatibility complex (MHC) class II alleles, and a variant of a heparanase gene have all been implicated in the multifactorial cause. The locus most commonly associated with immunogenetic susceptibility to neoplastic transformation and viral infections, MHC class I, has not been studied, however. Genomic DNA was extracted from skin samples of 20 cancer-positive and 40 cancer-negative sea lions. Using these samples, the MHC I gene sequence will be published, the MHC class I polymorphism will be assessed, and the association of specific MHC class I alleles with cancer-positive and cancer-negative sea lions will be determined. We hypothesize that particular MHC class I alleles that successfully present immunodominant peptides of the otarine herpesvirus-1 will be present in cancer-negative animals but not cancer-positive animals and that there will be increased homozygosity of MHC alleles in sea lions with carcinomas as compared to those without.
Differential mucins gene expression between respiratory human paramyxovirus infections (VIR5P.1142)
Authors: Banos-Lara Rocio , Guerrero-Plata Maria 
Published: January 2023

Abstract
Mucin (MUC) proteins are the main component of mucus and constitute part of the innate immune response. High production of mucins and mucus is characteristic in inflammatory lung diseases. Respiratory Syncytial Virus (RSV) and Human Metapneunovirus (hMPV) are RNA viruses belonging to the Paramyxoviridae family and represent the most important cause of severe lung diseases such as pneumonia and bronchiolitis in young children, the elderly and immunocompromised individuals. Although these viruses are close-related, the host immune response elicited by them is widely different. In this work we evaluated the lung gene expression of secreted (MUC2, MUC5AC, MUC5B, MUC8 and MUC19) and cell surface (MUC1, MUC3, MUC4, MUC13, MUC15, MUC16, MUC20, MUC21 and MUC22) mucins by qRTPCR in human epithelial cells infected with RSV or hMPV. Our data indicate that the MUC expression by RSV and hMPV differ significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21 and MUC22 by RSV infection at 48 and 72 h than by hMPV. On the other hand, the expression of MUC2, MUC5B and MUC1 was dominated by the infection with hMPV at the same time points. No significant MUC5AC, MUC19, MUC3, or MUC13 expression was observed after any of the infections. Together, these data indicate that RSV appears to be a stronger inducer of MUC response than hMPV and suggest that MUC expression contribute to the differential immune response induced by these two major human respiratory viruses
FasL-dependent regulation of the magnitude of the CD8 T cell response during lethal dose influenza virus infections (VIR5P.1144)
Authors: Zacharias Zeb , Legge Kevin 
Published: January 2023

Abstract
Our recent work has detailed a novel regulation of the IAV-specific CD8 T cell response during lethal dose or infection with high pathogenic IAV strains. During such infections, FasL+ plasmacytoid dendritic cells (pDC) within the regional lymph nodes (LN) target and eliminate the developing Fas+ effector T cell response, therein limiting immunity and driving severe disease. While our studies have shown that pDC are sufficient to drive this mechanism (i.e. transfer of wild type pDC into gld mice results in elimination of activated CD8 T cells), antibody targeted elimination of pDC in wild type mice does not completely halt CD8 T cell apoptosis. This suggested that an additional cell type might contribute to the overall loss of CD8 T cells during lethal/high path IAV infections. Herein we describe a novel cell population which shares some common markers with both pDC and B cells, but can be distinguished from both based on unique marker expression. These FasL+ cells are found at 4.5x greater numbers in the LN of lethal vs sublethal dose IAV mice and are 8.5x more prevalent than pDC with those LN. Further our results suggest that the FasL+ phenotype within this cell population segregates to BST2+ cells. Our current studies are focused on determining the factors regulating this novel cell population and it’s relative contribution to the overall FasL-dependent control of the magnitude of the CD8 T cell response during IAV infections.
Characterization of crossreactive T cell receptors that recognize both Epstein Barr virus and influenza A virus during acute influenza A virus infection (VIR5P.1135)
Authors: Song InYoung , Gil Anna , Stern Lawrence , Selin Liisa 
Published: January 2023

Abstract
Crossreactive CD8+T cells that recognize both influenza A (IAV) epitope M158, and Epstein Barr virus (EBV) epitope BRLF1109, are frequently found in HLA-A*02 populations particularly during acute infection. However, whether this crossreactivity is mediated by a single crossreactive T cell receptor (TCR) is unclear. To address this, M1- and BRLF1-MHCI oligomer positive CD8+T cells from peripheral blood of an acute IAV-infected patient who was EBV seropositive were single cell sorted and the TCR genes were sequenced and cloned. Thirty-three of 96 single cells yielded one TCRα and one TCRβ gene with 13 unique reproducible TCRα/β pairs. These 13 pairs of TCR genes were characterized in TCR deficient Jurkat cells expressing CD8α (J76) for antigen recognition and TCR signaling. In each case the transfected J76 cells bound strongly to M1-MHCI tetramer and weakly to BRLF1-MHCI tetramer consistent with the original staining in the peripheral blood. These crossreactive TCR-transfected J76 cells responded functionally to both peptides as they upregulated CD69 in response to BRLF1 as well as M1 peptide stimulation with four orders of magnitude difference. Interestingly, one TCR similar to JM22 which is a public TCR recognizing M1 epitope, was also crossreactive to BRLF1, which implies that many HLA-A*02 populations may be crossreactive to EBV. Our data clearly shows that crossreactivity between M1 and BRLF1 epitopes can be mediated by a single TCR and may be ubiquitous.
Age-related dysregulation in the lipidome compromises the immune response to the severe acute respiratory coronavirus (VIR5P.1140)
Authors: VIJAY RAHUL , Gelb Michael , Murakami Makoto , Perlman Stanley 
Published: January 2023

Abstract
Age-associated changes have long been known to cause dysregulation in antiviral immune responses. The SARS epidemic of 2002-03 was characteristic in this respect that it exhibited an age-associated increase in mortality. We recently reported that an age-related increase in an eicosanoid, prostaglandin D2 (PGD2) contributed to the observed higher mortality in SARS-CoV infected aged compared to young mice. To examine the factors that resulted in elevated levels of PGD2 in aged mouse lungs, we analyzed the gene expression levels of several enzymes in the eicosanoid pathway. Remarkably, secretory phospholipase A2 group 2D (Pla2g2d), which is preferentially expressed in lung CD11c+ cells, was significantly higher in aged compared to young mice. Lipid profiling of aged and young SARS-CoV-infected mice revealed that unlike young mice, aged mice failed to upregulate many pro-inflammatory lipid mediators although both groups upregulated the pro-resolving ones. Further, aged mice lacking PLA2G2D expression (Pla2g2d-/-) mice exhibited enhanced virus clearance, increased lung DC migration to the draining lymph nodes and increased virus specific T cell responses. Infection of aged Pla2g2d-/- mice with SARS-CoV increased survival from 20% to 80-90%, compared to Pla2g2d+/+ mice. Altogether our data identify a novel role for Pla2g2d in the lungs of aged mice in skewing the lipidome to an anti-inflammatory state and thus predisposing the animal to a worse outcome following SARS-CoV infection.
CX3CR1+ CD8 T cells in treated HIV infection are functionally impaired by platelet interactions (VIR6P.1171)
Authors: Freeman Michael , Mudd Joseph , Panigrahi Soumya , Lederman Michael 
Published: January 2023

Abstract
In the era of highly effective antiretroviral therapy (ART), HIV-infected patients have a better long-term prognosis than ever; however, increased inflammation and coagulation in HIV infection is associated with an increased risk of cardiovascular and other morbidities. CD8 T cell expansion is characteristic of HIV infection and has been linked to increased morbidities especially cardiovascular disease in treated HIV infection. Here we have identified a population of circulating memory CD8 T cells that express the vascular endothelium homing receptor CX3CR1 (fractalkine receptor) and is enriched in ART-treated HIV+ patients. CX3CR1+ CD8 T cells have elevated expression of the platelet-binding receptor PSGL-1 and the thrombin-activated receptor PAR-1, suggesting a possible role in cardiovascular disease via endothelial localization and interactions with platelets and mediators of coagulation. We found that even though thrombin stimulation via PAR-1 could directly enhance CD8 T cell responses in vitro, CD8 T cell cytokine production was diminished in the presence of thrombin-activated platelets through mechanisms mediated in part by TGF-β. Thus, we have identified a population of circulating memory CD8 T cells in HIV infection that are activated by thrombin, are susceptible to platelet-mediated regulation, and could contribute to cardiovascular disease risk in ART-treated HIV-infected patients.
Mouse polyomavirus-specific CD8+ T cells establish a brain-resident memory population during persistent infection (VIR6P.1174)
Authors: Frost Elizabeth 
Published: January 2023

Abstract
Human JC polyomavirus (JCV) causes progressive multifocal leukoencephalopathy (PML), a rare but life-threatening demyelinating disease in patients under profound immunosuppression and those receiving therapeutic immunomodulation for autoimmune and inflammatory disorders. Using persistent mouse polyomavirus (MPyV) infection in mice, we are developing a model of PyV-induced CNS disease to elucidate the role of immunosuppression in PML pathogenesis. Histology revealed corpus callosum demyelination in 100% of persistently infected mice. Following intracerebral injection with MPyV, immunocompetent C57BL/6 mice showed robust infiltration by MPyV-specific CD8 T cells with minimal contraction. During persistent CNS infection, a significant population of CD8 T cells exhibited a tissue-resident memory (Trm) phenotype (CD103+CD69+CD62Llo), as reported for acute VSV and latent HSV-1 infections, and incorporated BrdU in situ, suggesting capacity for self-renewal. Furthermore, these Trm cells develop and survive independently of replenishment by circulating antiviral CD8 T cells or CD4 T cell help. Unlike in the spleen, MPyV-specific CD8 T cells are PD-1hi upon infiltration of the brain without evidence of exhaustion. Interestingly, levels of CD8 and T cell receptor also increase on cells in the brain over time. Whether brain-infiltrating T cells exhibit higher sensitivity to antigen due to higher affinity and/or functional avidity is currently under investigation.
Strain differences in CD8 T cell expansion revealed in vivo during LCMV infection and ex vivo by TCR stimulation (VIR6P.1176)
Authors: Tarrio Margarite , Ploquin Mickael , Suarez-Ramirez Jenny , Biron Christine 
Published: January 2023

Abstract
Lymphocytic choriomeningitis virus (LCMV) infection of C57BL6 (B6) mice induces dramatic virus-specific CD8 T cell expansion. Comparison of B6 and 129-Sve (129) mouse strain responses demonstrated that the magnitude of total LCMV-specific CD8 T cell expansion was much lower in the 129 mice. The difference occurred even though viral titers and proportions of CD8 T cells specific for the three immunodominant epitopes of LCMV were similar. A higher type 1 IFN response was associated with the enhanced expansion in the B6 mice, and the responding CD8 T cells in B6 as compared to 129 mice had elevated levels of the signal transducer and activator of transcription (STAT) 4 but lower levels of the STAT1 molecule used to mediate inhibition of proliferation. The magnitude of the response was significantly diminished in B6 but not 129 mice genetically altered to block in IFN responsiveness, i.e. IFN receptor or STAT1 deficient, such that overall CD8 T cell expansion was now similar in both strains. Culture studies with purified cells demonstrated that in comparison to B6, 129 CD8 T cells had poor proliferative potential when stimulated through the TCR. Thus, intrinsic mechanisms linked to genetic differences regulate the magnitude of CD8 T cell proliferation. The data suggest that these differences have consequences for type 1 IFN requirements in shaping the magnitude of the response and overall immunity to viral infections. Supported by the National Institutes of Health, USA.
The effect of staphylococcal enterotoxin B on antiviral CD8+ T cell responses (VIR6P.1177)
Authors: Meilleur Courtney , Memarnejadian Arash , Haeryfar S. M. 
Published: January 2023

Abstract
Staphylococcal enterotoxin B (SEB) is a bacterial superantigen capable of activating a large percentage of the T cell repertoire. Contact with SEB causes T cells to proliferate and secrete inflammatory cytokines, ultimately resulting in deletion or anergy of the activated T cell. This may leave holes in the T cell repertoire, altering the ability of the host to respond to viral infection. We have used a mouse model of influenza (IAV) vaccination and infection to gauge the effect of SEB administration on the quality of the antiviral CD8+ T cell response. Our results show that SEB alters the immunodominance hierarchy of epitope-specific CD8+ T cells during primary, memory and recall responses. We also found that these changes can be explained by the presence or absence of SEB-reactive Vβ regions in the TCRs of epitope-specific CD8+ T cell populations. Intriguingly, SEB exposure also augments the ability of one epitope-specific CD8+ T cell population to kill their target cells. Contrary to previous reports, these results show that contact with SEB may enhance CD8+ T cell responses in the context of IAV infection. In summary, our work uncovers a novel effect of SEB on the immune system, one that has potentially useful implications for the treatment of viral diseases.
Paradigm-violating HLA class II-restricted CD8 T cells exist in HIV infected individuals (VIR6P.1164)
Authors: Ranasinghe Srinika , Lamothe Pedro , Damien Soghioan , Jones Brad , Sidney John , Sette Alessandro , Streeck Hendrik , Picker Louis , Kappler John , Kaufmann Daniel , Walker Bruce 
Published: January 2023

Abstract
The T cell paradigm dictates that CD8 T cells recognize peptides presented by MHC class I. Yet, class II-restricted CD8 T cells were recently observed in rhesus macaques vaccinated with a RhCMV/SIV vector (reviewed in Ranasinghe and Walker 2013 Nat Biotech). Restriction of CD8 T cells by class II is rare, with less than a dozen published studies in two decades. Our study aimed to assess whether class II-restricted CD8 T cell responses exist in HIV infection. We detected class II-restricted CD8 T cells in 3 HIV infected individuals. The responses were identified using a novel 'HLA-DRB1 ELISpot' where patient CD8 T cells were co-cultured with HIV peptide-pulsed mouse LCL expressing human recombinant DRB1 (N=2/30 DRB1*01 and N=1/22 DRB1*11 subjects). Antibody blocking of class I and II, and class II tetramer binding confirmed the DRB1 restriction. Strikingly, up to 12% of total CD8 T cells bound class II tetramer directly ex vivo. The class II-restricted CD8αβ T cells expressed a TEMRA phenotype with a distinct polyfunctional profile and single TCR vBeta clonotype when compared intra-patient to class I-restricted CD8 TEM responses. Class II-restricted CD8 T cells exhibited high levels of Perforin and Granzyme B and efficiently lysed peptide-pulsed autologous BCL and CD4 T cells, yet showed impaired killing of autologous HIV-infected CD4 T cells in vitro. In our study, we have demonstrated the first proof-of-principle detection of class II-restricted HIV-specific CD8 T cells.
A virus-encoded miRNA in mouse polyomavirus regulates viral replication in the kidneys in a CD8 T cell dependent manner. (VIR6P.1166)
Authors: Maru Saumya , Lukacher Aron 
Published: January 2023

Abstract
The polyomaviruses JCV and BKV are ubiquitous DNA viruses in the human population which persist as low-level infections in host kidneys and give rise to disease upon immunosuppression, resulting in significant morbidity and mortality. The polyomaviruses encode one endogenous miRNA, with both the 5p and 3p mature miRNAs functioning to reduce levels of target transcripts. The mouse polyomavirus (MPyV) also encodes a miRNA within the sequence for the early nonstructural proteins large (LT) and middle (MT) T-antigen, both of which have been established as miRNA targets. Other targets of the MPyV miRNA and their physiologic consequences have been poorly defined. The dl1013 virus is a deletion mutant of MPyV which eliminates expression of the endogenous miRNA while preserving LT and MT functions vital to the viral life cycle. We have shown that infecting immunocompetent C57BL/6 mice with dl1013 results in lower viral levels in the kidneys than infection with parental virus, but not in other organs. No difference in kidney viral levels between parental and dl1013 virus is seen in CD8α-/- mice, suggesting that the effect of the miRNA on viral replication is dependent on CD8 T cells. We are currently investigating whether this MPyV miRNA affects recruitment of myeloid and lymphoid cells into the kidney and their role in controlling MPyV in the dominant reservoir of viral persistence of both human and mouse polyomaviruses.
Identification of ribosomal proteins as targets for protective CD4+ T cell responses against mycobacteria (APP5P.114)
Authors: Johnson Alison , Kennedy Steven , Lindestam Arlehamn Cecilia , Hegde Subray , Seidel Ronald , Blanchard John , Sette Alessandro , Chan John , Jacobs William , Porcelli Steven 
Published: January 2023

Abstract
Mycobacterium tuberculosis (Mtb) infects one-third of the global population, and a more efficacious vaccine is urgently needed for control and prevention of disease caused by Mtb. We previously reported a genetically modified strain of Mycobacterium smegmatis called IKEPLUS, which is a promising vaccine candidate due to its ability to generate an unprecedented level of bactericidal immunity against Mtb in mice. Protective immunity induced by IKEPLUS is dependent on antigen-specific CD4+ T cell memory, and we hypothesized that specificity of the CD4+ T cell response was a critical feature of this protection. Using in vitro assays of IFNγ production by splenocytes from IKEPLUS-immunized mice, we identified an immunogenic peptide within the mycobacterial RplJ protein encoded by the Rv0651 gene. In a complementary approach, screening T cell hybridomas against Mtb ribosomal proteins identified as the RplA protein, a product of the Rv0641 gene in Mtb, as an additional specific target. Both RplJ and RplA are structural proteins of the 50S large subunit of the mycobacterial ribosome. Our results demonstrate that the CD4+ T cell response in IKEPLUS-immunized mice has multiple targets including components of the mycobacterial ribosome, among which RplA and RplJ represent novel specificities for protective responses against Mtb. Further studies to more fully define the CD4+ T cell responses to ribosomal targets should help to inform the design of effective vaccines against Mtb.