bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effector lymphocytes induce lymph node-like vasculature in tumors, which enables naïve T cell infiltration and enhanced anti-tumor immunity (TUM7P.1020)
Authors: Peske J , Thompson Elizabeth , Gemta Lelisa , Baylis Richard , Fu Yang , Engelhard Victor 
Published: January 2023

Abstract
Intratumoral lymph node (LN)-like vasculature, characterized by the expression of peripheral node addressin (PNAd) and chemokine CCL21, has been correlated with T cell infiltration and a positive prognosis in breast cancer and melanoma patients. However, the mechanisms controlling its development, and how it contributes to a beneficial outcome for cancer patients, are unknown. Here we demonstrate that LN-like PNAd+ CCL21+ vasculature develops in murine models of melanoma and lung carcinoma growing in multiple anatomic locations. PNAd expression on tumor-associated endothelium and CCL21 expression by tumor-associated endothelial cells and gp38+ fibroblasts was controlled by a novel mechanism dependent on tumor infiltrating effector lymphocytes that secreted LTα3. In intraperitoneal (IP) tumors, CCL21 was also controlled by IFNγ. While effector CD8 T cells induced LN-like vasculature in both subcutaneous (SC) and IP tumors, NK cells only promoted its development in SC tumors. In IP but not SC tumors, LN-like vasculature was associated with organized aggregates of B-lymphocytes and gp38+ fibroblasts that resembled tertiary lymphoid organs. Importantly, this LN-like vasculature enabled the infiltration of adoptively transferred naïve T cells. These T cells underwent activation and effector cell differentiation in the tumor, and significantly delayed tumor outgrowth. These results establish LN-like vasculature as both a consequence of and key contributor to anti-tumor immunity.
Anti-CEA chimeric antigen receptor T cells in combination with suppressor cell targeting for the treatment of colorectal cancer peritoneal metastases (VAC7P.1043)
Authors: Point Gary , Thorn Mitchell , Cunetta Marissa , Bais Anthony , Boutros Cherif , Hanna Nader , Espat N , Junghans Richard , Katz Steven 
Published: January 2023

Abstract
Colorectal peritoneal metastases (PM) is a grave condition in which tumor cells disseminate throughout the abdomen. Chimeric antigen receptor T cell (CAR-T) immunotherapy is a promising therapy for PM. We developed a novel regional delivery approach to maximize CAR-T efficacy against PM while limiting systemic toxicity. Murine tumor cells expressing CEA and luciferase were injected intraperitoneally (IP) in mice to induce PM (day 0). We injected murine anti-CEA CAR-T IP on days 3 and 6, alone or in combination with antibodies against Ly6G/Ly6C, PDL1 or GITR to target myeloid suppressor cells (MSC) or regulatory T cells (Treg), which we have shown to be present in PM. Tumor burden was measured by bioluminescence. In comparison to unmodified T cells, CAR-T alone mediated a 22-fold reduction of tumor burden (p=0.028). The combination of CAR-T with anti-PDL1, anti-GITR or anti-Ly6G/Ly6C treated groups showed 25-fold, 104-fold and 153-fold reductions, respectively. The CAR-T + anti-GITR and CAR-T + anti-Ly6G/Ly6C groups had a significantly better treatment response than CAR-T alone (p=0.005 and p=0.017). On days 8 and 10, CAR-T + anti-Ly6G/Ly6C tumor burdens dropped below detectable levels. Upon gross inspection, CAR-T treated mice did not have detectable tumor. Our findings demonstrate that targeting MSC and Treg in addition to regional IP CAR-T delivery represents a viable immunotherapeutic strategy that resulted in complete responses in mice with established PM.
Effects of trans-sialidase enzyme activity, secretion and antigen persistence on the induction of protective immunity against Trypanosoma cruzi infection (VAC8P.1054)
Authors: Cai Catherine , Guo Hongjie , O'Shea Anne , Eickhoff Christopher , Beverley Stephen , Hoft Daniel 
Published: January 2023

Abstract
Chagas Disease is a life-threatening illness caused by chronic infection with the Trypanosoma cruzi parasite. It affects up to 11 million people in Latin America, where it is a leading cause of heart disease, making vaccine development critical and worthwhile. Because the T. cruzi trans-sialidase (TS) enzyme is highly conserved and necessary for parasite virulence, it has strong potential as a vaccine target. We have shown that mice can be protected by vaccination with dendritic cells pulsed with a single pair of immunodominant TS epitopes, validating further exploration of TS as a target. We recently have generated live vaccines by transfecting Leishmania major with four TS variations: active secreted, active non-secreted, inactive secreted and inactive non-secreted. These also were transfected into an avirulent, dihydrofolate reductase knock-out strain of Leishmania to investigate the role of antigen persistence versus clearance on immune response. Mice will be infected with the recombinant Leishmania and later challenged with T. cruzi to analyze protective immunity. In preliminary experiments, recombinants were found to express the TS protein and immunizations protected BALB/c mice from infection. This project is the first examining the ability of recombinant Leishmania to serve as vaccine vehicles for Chagas Disease. These experiments will also elucidate the relative importance of inducing central and peripheral memory T cell populations for protective T. cruzi immunity.
Enhancing pulmonary function in women with lymphangioleiomyomatosis through exercise training (VAC9P.1109)
Authors: Lowder Thomas 
Published: January 2023

Abstract
Lymphangioleiomyomatosis (LAM) is a rare disease affecting women almost exclusively. There is no cure for LAM and few treatment options other than immunosuppressive drugs (e.g. sirolimus, everolimus) exist. Rather than attempting to cure LAM, our lab is focused on reversing declines in pulmonary function through aerobic exercise training. A total of 11 patients are enrolled (age from 27 to 59). Following initial assessments of pulmonary function testing, exercise capacity, and bone mineral density, patients underwent individualized, supervised exercise training (2d/wk). Every 3mo patients were reassessed for changes in the above measures. All patients improved in exercise tolerance (time to fatigue, increased work capacity) and in oxygen consumption (VO2max) following training. Most patients showed an improvement in pulmonary function measures (FEV1, FEV1/FVC) and in bone mineral density, both whole body and lumbar vertebrae. FVC increased in several patients. Anecdotally patients reported improvements in daily living tasks (energy levels, decreased dyspnea upon exertion) and quality of life measures (lower levels of depression, greater outlook on life, improved overall mood). This is the first non-drug intervention to show improvements in pulmonary function in this patient population. Although this study is not yet complete, preliminary results suggest that exercise training only two days per week can result in substantial improvements in patients with LAM.
Characterization of class II β chain major histocompatibility complex genes in a family of Hawaiian honeycreepers: ‘Amakihi (Hemignathus virens) (VET1P.1124)
Authors: Jarvi Susan , Farias Margaret , Bianchi Kiara , Txakeeyang Ann , MacFarland Thomas 
Published: January 2023

Abstract
The objective of this study was to estimate the number and degree of variation of Mhc class II β chain genes and alleles in a family of Hawaiian honeycreepers (`Amakihi, Hemignathus virens). The parents were bred in captivity and produced eight progeny. Partial antigen binding region (173 bp) fragments were produced via PCR+1 cloning and sequenced on a Beckman CEQ system, and two Roche 454 platform pyrosequencing runs. A total of 302 sequences were obtained via cloning. After quality filtering and removal of chimeras, a total of 2762 sequences were retained from 454 run 1 and 3958 sequences from 454 run 2. Unique sequences detected &lt;3 times within an individual were discarded. All sequences were used to generate a neighbor-joining tree in MEGA v. 5.2 to evaluate sequences across family members. Singlet sequences were discarded. The remaining sequences were used to evaluate segregation and relationships of loci. A total of 19 putative loci were detected in this family. Allelic segregation was not observed among any of these loci thus they appear to be independent, but linkage was observed among four loci suggesting segregation of a haplotype among 5 progeny. The finding of 37 sequences in one individual also suggests a minimum of 19 Mhc class II loci in `Amakihi. Of these, 17 loci are classical Mhc loci thus designated as DAB, but mean diversity and evolutionary divergence values among groups suggest that two loci are non-classical and thus should be designated as DBB.
The complex of damage-associated molecular pattern and its inducer, pathogen-associated molecular pattern enhance triggering innate immunity in shrimp (VET1P.1128)
Authors: Chen Jiann Chu 
Published: January 2023

Abstract
Peptidoglycan (PG) derived commonly from Gram-positive bacteria, is one of pathogen-associated molecular pattern (PAMP). Incubating hemocytes of shrimp in PG caused degranulation, changes in cell size, reduction in the percentage of cell viability, necrosis of hemocytes, and released intracellular molecules containing damage-associated molecular pattern (DAMP) that is well known in mammals and teleosts. Incubating shrimp hemocytes in PAMP, DAMP or the mixture of PAMPs plus DAMPs all induced significant increases in phenoloxidase (PO) activity and respiratory burst (RB, release of superoxide anion) in vitro. The PO activity and RB induced by the mixture of DAMP-PAMP were much greater than that induced by DAMP alone or PAMP alone. In conclusion, the mixture of DAMP-PAMP cause enhancement in eliciting innate immunity of shrimp. This is the first study to confirm that cell necrosis caused by PAMPs releases intracellular molecules, DAMPs, and the mixture of DAMP-PAMP elicit the innate immunity in an invertebrate.
The role of mobile elements in the evolution of pathogen-sensing gene clusters in coral (VET1P.1129)
Authors: Garrison Keith , Moore Christine 
Published: January 2023

Abstract
While the molecular mechanisms of coral immune responses are unclear, the Acropora genome reveals complex gene networks associated with innate immunity, apoptosis, and autophagy. We are interested in whether mobile genetic elements help drive the evolution of disease resistance gene clusters in corals. The purpose of this project is to mine the coral genome for pathogen recognition and disease resistance loci in the leucine-rich repeat (LRR) and immunoglobulin (Ig) families to map and analyze regions with an increased density of these genes. Pfam searches in the A. digitifera genome for Ig and LRR loci were performed. Ig- or LRR-containing regions were clustered based on genome location/scaffold position, and the resulting genome sequence region was extracted. The identities of the translated protein sequences within the extracted regions were determined using BLAST. LRR or Ig designations were annotated onto their corresponding open reading frame sequences. CENSOR was used to detect and annotate mobile element sequences within each cluster. We built phylogenetic trees to analyze relationships of the LRR and Ig loci within and between these clusters to determine whether similar mobile element sequences were associated with the amplification and dissemination of disease resistance loci. We found related resistance gene sequences associated with similar mobile element sequences both within and across resistance gene clusters.
Differentially expressed immune related genes in bovine neonatal development (VET1P.1114)
Authors: Pasman Yfke , Merico Daniele , Kaushik Azad 
Published: January 2023

Abstract
A thorough understanding of the developing bovine neonatal immune system is important for the development of novel vaccines and therapeutics, as well as to improve breeding practices and farm management, in order to increase the survival and productivity of calves. In this study blood samples were taken from neonates on day of birth before colostrum feed (day 0), and at 7, 14 and 28 days after birth. RNA was extracted from peripheral blood mononuclear cells present in the samples and processed for next generation sequencing. An average of 27 million 151bp reads per sample was generated, and global analysis of the whole transcriptome was performed, based on Hereford cow genome assembly UMD3.1. Differential expression analysis (DE) of immune response related genes were performed at each time point, as well as gene-set enrichment analysis to identify DE genes in immune related pathways comparing day 0 and 7. The analysis identified several immune response related functional coherent DE gene-sets, for example: immune response, defense response, regulation of defense response, cytokine production, and response to cytokine. Within these clusters, the genes with significantly altered expression rates (False Discovery Rate FDR&lt;0.05) and logFC&gt;1 or logFC&lt;-1) were identified. These studies will help to elucidate the mechanisms that are important in bovine neonatal immune development, which will contribute to the development of targeted strategies for disease prevention.
Deciphering the adaptive immune system of bats (VET2P.1131)
Authors: Martínez Gómez Julia , Wang LinFa , Alonso Sylvie 
Published: January 2023

Abstract
Bats are natural reservoirs for several viruses, many of which cause morbidity and high mortality rates in other mammals, including humans but they generally don’t cause disease in bats. In fact, fruit bats have been found to be the principal suspect that initiated the latest 2014 West-Africa Ebola outbreak. How bats cope with such deadly viruses without getting sick remains unknown. Efforts are being increasingly devoted to dissect the bat’s immune system, however, due to the lack of reagents progress has been limited. Our group is focusing on characterizing bats adaptive immunity. The first step consists of generating a systematic knowledge on the various immune cell populations (T and B cells mainly). Subsequently, functional assays will be optimized to study how bats adaptive immunity reacts to viral infections. Screening of human and mouse antibodies against the main components of the bats adaptive immunity revealed poor cross-reactivity to T and B cell main surface markers (CD3, CD4, CD8, CD19). Combining flow cytometry and real-time PCR approaches, we have been able to characterize different T cell subset populations present in bats spleen and blood. Understanding how bats control viral infection can provide important insights into anti-viral strategies that may result in the development of new therapeutics for other mammals
Generalised inflammation with CD3ε and MHC class II positive cells and dislocated epithelial cells in the mid-intestine in farmed Atlantic salmon (Salmo salar L.) (VET2P.1132)
Authors: Bjørgen Håvard , Koppang Erling , Kaldhusdal Magne , Moldal Torfinn , Dale Ole-Bendik 
Published: January 2023

Abstract
Farmed Atlantic salmon is routinely fed with pellets containing vegetable ingredients. Certain plant proteins may induce an inflammatory environment in the intestinal tract of fish, and carcinogenesis has also been noted. The pathogenesis is similar to that of inflammatory bowel disease (IBD)-related cancer in humans. A feed trial was designed to stimulate to inflammation in experimental fish. Three separate groups were subjected to feeding regimes where two of the groups received feeds containing different plant ingredients (A and B), and a third group received a diet based on marine ingredients. Immunofluorescence targeting CD3ε and MHC class II were used to study the inflammation. Epithelial cells were identified with haematoxylin & eosin staining and immunohistochemistry. A pan cytokeratin antibody was used to identify epithelial cells, and a proliferating cell nuclear antigen (PCNA) antibody was used to mark proliferating cells. Periodic acid Shiff (PAS) staining was used to detect mucins. Immunofluorescence revealed severe generalised inflammation and various amounts of dislocated epithelial cells in the fish receiving experimental diet B. The fish given experimental diet A was less affected. The control group was unaffected. There was a clear association between inflammation and dislocated epithelial cells. The inflammatory response was dominated with T-cell infiltrates in a similar fashion as that seen in IBD-affected human intestine.
Extensive cell-mediated cross-reactivity between diverse influenza strains in the ferret model (VIR5P.1143)
Authors: Reber Adrian , Music Nedzad , York Ian 
Published: January 2023

Abstract
Influenza causes widespread epidemics affecting the world’s population. The virus achieves this on a yearly basis due to its ability to escape prior immunity by rapidly mutating surface proteins, the target of neutralizing antibodies. In contrast, the internal viral proteins, targets of the cell-mediated immune (CMI) response, are highly conserved, and have potential for cross-protection. However, little has been done to comprehensively evaluate the true extent of CMI cross-reactivity between influenza strains. Unvaccinated or vaccinated ferrets were challenged with 2008-2009 pandemic H1N1 influenza, A/Perth/16 (H3N2), or mock challenged. Cellular responses were examined 14d post-infection by stimulation with a diverse array of influenza viruses, and IFN-γ production by CD8+ and CD4+ T cells was assessed by flow cytometry. CMI responses exhibited extensive cross-reactivity across the majority of strains examined, but not to an unrelated virus, canine parainfluenza. Cross-reactivity was observed even between influenza A and B strains. While prior vaccination had little effect on the breadth of cross-reactivity, cross-reactive CD4+, but not CD8+ responses were heightened by prior vaccination. Challenge with pandemic H1N1 drove better cross-reactivity with B strains. These results confirm the widely held belief that CMI responses exhibit extensive cross-reactivity and extend this concept to strains considered antigenically distant such as influenza A and B strains.
Human γδ T cells: diverse orchestrators of the host response to influenza infection. (VIR5P.1145)
Authors: Calverley Matthew , McClaren Jennifer , GUO XIZHI , Dash Pradyot , Thomas Paul 
Published: January 2023

Abstract
While often mild, influenza infection can occasionally progress to severe disease and even death. It is recognized that disease progression and outcome is often worse in the young and the old; however, the reason infection progresses in some individuals and not others is still unclear. Previous findings, reported by our laboratory, from a five-year longitudinal human study have shown that a definable inflammatory cytokine signature correlates with poor clinical outcome. Moreover, we have shown that this cytokine profile correlates with inflammatory monocyte numbers. Here we show a correlation between γδ T cell numbers and inflammatory monocyte numbers during infection within this clinical cohort. Further, we show that a subset of peripheral γδ T cells exhibit a surprisingly high T cell receptor (TCR) variable region gene diversity in infected individuals. Additionally, the CDR3 TCR sequences of this cellular subset show very high diversity, while retaining repetitive VJ gene junction-determined conserved motifs. The data presented here suggest that human peripheral γδ T cells are a more diverse cellular population than previously realized and are capable of playing a pivotal role in influencing the local immune environment during influenza infection with the potential to effect long-term outcome.
Age-related prevalence of serum hemagglutination-inhibition antibodies cross-reactive to 2012 and 2013 newly emerging swine-origin influenza A(H3N2) variant viruses (VIR5P.1134)
Authors: Liu Feng , Veguilla Vic , Gross Felicia , Levine Min , Xu Xiyan , Tumpey Terrence , Katz Jacqueline , Lu Xiuhua 
Published: January 2023

Abstract
Recent outbreaks of swine-origin influenza A(H3N2) variant virus (H3N2v) in the U.S., mainly among young children with swine exposure, have raised concerns. Previous studies demonstrated older children and young adults had the highest hemagglutination-inhibition (HI) antibodies (Ab) to 2011 H3N2v viruses. In 2013, newly emerging antigenic variants of H3N2v viruses, responsible for 18 human infections, acquired N145K/R mutations in hemagglutinin (HA). Here, human and postinfection ferret sera were tested in HI assays against 2012-13 H3N2v viruses possessing 145N, K or R HA mutations, together with nine historical seasonal H3N2 (sH3N2) viruses circulating since 1968. We found the H3N2v viruses were antigenically distinct but retained a low degree of serologic cross-reactivity (CR) (with ferret antisera) to sH3N2 viruses that circulated in 1990s. Across all age groups (6-80+ years), approximately half were seropositive (HI titer≥40) to the H3N2v viruses. The age related seroprevalence among children were likely associated with primary exposure to sH3N2 viruses in 1990s. We observed a single substitution at 145 in HA was sufficient to change an individual’s seropositivity to the virus and significantly influenced the seroprevalence in certain age groups. The susceptibility to 2012-13 H3N2v viruses remains high in young children, and low in older children and young adults. Improved knowledge of age-related CR Ab is critical for influenza risk assessment and pandemic preparedness.
MicroRNA-30c is utilized by PRRSV in immune evasion through targeting JAK1 in the type I interferon signaling pathway (VIR5P.1153)
Authors: Zhang Qiong , huang chen , yang qian , Gao Li , Liu Hsiao-Ching , Tang Jun , Feng Wen-hai 
Published: January 2023

Abstract
Innate immune responses constitute the first line of defense against viral infections, and many viruses are capable of interfering with IFN signaling to escape from the innate immune responses and facilitate their proliferation and spread. Here, we found that a host miRNA, miR-30c, was up-regulated by porcine reproductive and respiratory syndrome virus (PRRSV) via activating NF-κB and benefited its infection. Subsequently, we demonstrated that miR-30c impaired the type I interferon (IFN-I) signaling pathway by targeting JAK1, resulting in the enhancement of PRRSV infection. To our knowledge, this is the first report of a host miRNA that suppresses IFN-I signaling by targeting JAK1, a vital component in the signaling of IFN-I. In addition, we found that miR-30c targeting sequences in JAK1 were conserved throughout mammals, and miR-30c was able to enhance both DNA virus (Herpes simplex virus) and negative-strand RNA virus (influenza virus) replications. Moreover, miR-30c is induced by IFN-I and acts as a negative feed-back modulator. These broad spectrum results suggest that miR-30c sets host IFN-I signaling response a threshold and is a universal regulator of viral replication. Our findings thus improve our understanding of the pathogenesis of PRRSV infection by identifying a new strategy whereby PRRSV to escape IFN-I-mediated antiviral immune responses by engaging miR-30c.