bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological characterization of tumor-associated macrophages in patients with different stages of hepatocellular carcinoma (HCC) (TUM4P.914)
Authors: Tsuchimoto Yusuke , Asai Akira , Yokohama Keisuke , Ohama Hideko , Suzushi Tetsuya , Fukunishi Shinya , Tsuda Yasuhiro , Higuchi Kazuhide , Kobayashi Makiko , Suzuki Fujio 
Published: January 2023

Abstract
Tumor-associated macrophages, major leukocytes detected in tumor tissues, have been characterized as M2Mφ. Recently, M2Mφ have been classified into different subsets; M2aMφ, M2bMφ and M2cMφ. Therefore, in this study, the subset of M2Mφ present in tumor tissues of HCC patients was determined. Tumor tissues were obtained by liver biopsy and liver resection from patients with early and advanced stages of HCC. Paraffin embedded tissue specimens were stained for PE-conjugated anti-CD68 Ab. Also, the same tissue specimens were stained for FITC-conjugated anti-IL-12 Ab, PE-conjugated anti-IL-10 Ab, FITC-conjugated anti-CCL1 Ab, and FITC-conjugated anti-CD206 Ab. Stained histologic specimens were examined microscopically. In the results, large numbers of CD68+cells were predominantly present in the edge of the tumors. Large numbers of Mφ were not isolated from the tumor nests. CD68+cells isolated from advanced stage HCC patients were determined as IL-10+CD206+ cells, while a few numbers of these cells were demonstrated in the tumor tissues of early stage HCC patients. IL-10+CCL1+ cells and IL-12+CD68+ cells were not isolated from both advanced stage and early stage HCC patients. These results indicate that a majority of M2Mφ present in advanced stage HCC patients are M2aMφ and/or M2cMφ.
Role and association of CD11b and Gr1+ cells in promotion of spontaneous lung cancer metastasis (TUM4P.920)
Authors: Sharma Rajesh , Chheda Zinal , Jala Venkatakrishna , Satpathy Shuchismita , Haribabu Bodduluri 
Published: January 2023

Abstract
Microenvironment plays an important role in tumor growth and metastasis. We established a unique metastasis model by in vivo passaging the Lewis lung carcinoma (3LL) cells with 7-11 days of culture in between passages. When injected subcutaneously the parental (3LL) cells have minimal metastasis whereas the in vivo passaged (p3LL) cells showed robust metastasis. The goal of this study is to identify the immune population that enhances the metastatic propensity of tumor cells. Purified p3LL (CD45-) cells also yielded similar metastasis excluding a direct role of residual immune cells in promotion of metastasis. The p3LL cells metastasized at similar frequency in WT and Rag2-/- mice indicating that adaptive immune cells are not required for metastasis. Analysis of tumors derived from 3LL vs p3LL revealed differential accumulation of CD11b+Gr1+ subpopulations. 3LL tumors contained higher CD11b+ Gr1high cells whereas p3LL tumors showed higher levels of CD11b+ Gr1low population. Interestingly, when CD11b+ Gr1low populations were isolated from spleen of p3LL tumor bearing mice and co-cultured with 3LL cells for 5 days, these cells acquired enhanced metastatic capacity as compared to control 3LL cells. These results indicate a distinct association and a critical role of CD11b+ Gr1low population in promotion of metastatic phenotype and suggest that abundance of CD11b+ Gr1low population may serve as a marker and a potential therapeutic target for inhibiting Lung cancer metastasis.
Activation of dendritic cells by soypeptide lunasin as a novel vaccine adjuvant (VAC6P.942)
Authors: Tung Chun-Yu , Flores Sarah , Han Ling , Yao Shuyu , Zhou Baohua , Sun Jie , Chang Hua-Chen 
Published: January 2023

Abstract
Adjuvants enhance the immunogenicity of vaccines and improve the immune responses. FDA approved aluminum is known to promote Th2 immune response, which is the most used adjuvant in human vaccines; however it is less efficient on eliciting cellular immune responses. Thus, any agent capable of modulating the immune responses is the key to develop efficacious vaccines. We have identified a new use of soypeptide lunasin as a novel immune modulator. The objective is to define the effectiveness of lunasin as an adjuvant on activating immune responses. Human peripheral blood mononuclear cells of normal donors were stimulated with various concentrations of lunasin followed by phenotypic analysis of DC subsets. Lunasin-treated conventional DCs (cDCs) not only expressed elevated co-stimulatory molecules (CD86) but up-regulated chemokines (CCL2, CCL3, CCL4) and cytokine (IL-1β). Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when comparing with medium control treatment in mixed lymphocyte reaction. In addition to cDCs, pDCs responded to lunasin stimulation as evidenced by IFNa production. Lunasin administration increased CD86 expression in cDCs and induced IFNa production by pDCs in mice. Moreover, immunization with OVA and lunasin in mice improved survival against OVA-expressing influenza virus. Our data suggest that lunasin may act as an adjuvant by targeting both cDCs and pDCs to enhance and modulate immune responses to vaccine antigens.
Parvovirus-mediated aplastic crisis and the virus-specific immune response in patients with sickle cell disease (VAC6P.948)
Authors: Penkert Rhiannon , Tang Li , Thomas Paul , Rosch Jason , Hurwitz Julia , Hankins Jane 
Published: January 2023

Abstract
Parvovirus infection, which is typically subclinical in healthy individuals, can have catastrophic effects in patients suffering from sickle cell disease (SCD). Infection disrupts erythropoiesis, often resulting in aplastic crisis and other life-threatening complications in patients with SCD. Attempts to develop a safe and effective parvovirus vaccine have yet to be successful and may be improved by a better understanding of natural immune responses to parvovirus infections. St. Jude Children's Research Hospital houses one of the largest centers for pediatric SCD in the United States and is therefore uniquely positioned to monitor immune functions in patients with SCD. Here, we describe a retrospective analysis of patient records, examining parvovirus-specific antibody results from a semi-quantitative, commercially-available ELISA as a function of time relative to aplastic crisis. Results showed: (i) frequencies of seropositive immune responses in patients with SCD of various age groups were comparable to those of healthy controls, (ii) parvovirus-specific immune responses were rapidly induced in patients following aplastic crisis, and (iii) responses were generally sustained for years after the aplastic crisis event. Ongoing studies include further dissection of adaptive and innate immune responses toward parvovirus infections in this patient population to help define correlates of protection against parvovirus disease.
Parasite-neutralizing and protective antibody response in macaques immunized with synthetic LbL microparticle vaccines containing the conserved T1BT* epitope of Plasmodium falciparum (VAC7P.976)
Authors: Powell Thomas , Tang Jie , Jacobs Andrea , DeRome Mary , Palath Naveen , Cardenas Edwin , Boyd James , Nardin Elizabeth , Kaba Stephen , Lanar David 
Published: January 2023

Abstract
We have previously shown that synthetic LbL-MP vaccines containing the conserved T1B repeat and T* epitopes from the P. falciparum circumsporozoite (PfCS) protein elicit a protective antibody response in mice. Immunogenicity and efficacy of these LbL-MP were tested in a non-human primate model, the rhesus macaque. LbL-MP were loaded with T1BT* peptide with or without covalently-linked Pam3Cys, a TLR2 ligand. Both constructs elicited T1B-specific antibody responses and T1BT*-specific T-cell responses dominated by IFNγ secretion with little or no IL-5 secretion. The Pam3Cys-modified construct was more potent, generating antibody responses that neutralized wild-type P. falciparum in an in vitro hepatocyte invasion assay. In addition, IgG was purified from the macaque immune sera and passively administered to naïve mice that were then challenged with 5,000 transgenic P. berghei sporozoites that expressed the full-length PfCS protein. IgG from individual macaques immunized with Pam3Cys.T1BT* LbL-MP protected mice from challenge, with 50-88% of mice parasite-free for ≥ 15 days. These results demonstrate that synthetic LbL-MP vaccines bearing the conserved T1BT* epitopes of PfCS can elicit protective antibody responses against P. falciparum in a non-human primate model.
Efficacy of a vaccine for Angiostrongylus costaricensis against rat lungworm disease caused by A. cantonensis in wild Hawaiian Rats (Rattus rattus) (VAC7P.978)
Authors: Jarvi Susan , Pitt Will , Osuna Antonio , Farias Margaret , Shiels Laura , Howe Kay , Jacquier Steven , Shiels Aaron , Amano Karis , Luiz Blaine , Maher Daisy , Allison Maureen , Holtquist Zachariah , Scheibelhut Neil , Severino Michael , Riddick LaTasha 
Published: January 2023

Abstract
The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen which causes a global, emerging infectious disease known as rat lungworm disease (RLWD). RLWD has been reported in 30 countries, and Hawaii is the epicenter for RLWD in the United States. We conducted a study in wild Hawaiian rats (Rattus rattus) to determine the efficacy of a vaccine developed against a related species (A. costaricensis). Twenty-eight wild adult rats were captured from Waiakea Forest Reserve on the Island of Hawaii. Rats were mated and 41 F1 offspring were vaccinated with two doses of PP2A vaccine, a serine/threonine phosphatase 2A recombinant peptide (4 µg vaccine and 4 µg adjuvant/25 g body weight) at &gt;3 mos. of age. Rats were gavaged with 50 L3 stage larvae at four weeks post-vaccination. Rats were euthanized and necropsies conducted at 51-53 days PI. Spleen weight, spleen length, and lung weight were recorded and number of worms in heart and lungs counted. Adult worms were found in all F1 rats. An average of 20.88 worms/rat reached adulthood with an infective dose of 50 L3 stage larvae. We found no significant differences between vaccinated rats (n=21) and unvaccinated rats (n=20) in spleen weight (p=0.963), spleen length (p=0.830), lung weight (p=0.830) or number of worms collected from the heart and lungs (p=0.882), suggesting the vaccine does not provide adequate protective immunity to guard against infection by A. cantonensis in wild Hawaiian rats.
Rectal immunization with an rVCG vaccine protects against genital Chlamydia challenge (VAC7P.962)
Authors: Pais Roshan , Jha Rajneesh , Omosun Yusuf , He Qing , Fujihashi Kohtaro , Black Carolyn , Igietseme Joseph , Eko Francis 
Published: January 2023

Abstract
Pelvic inflammatory diseases consequent to Chlamydia trachomatis infections is a major public health challenge with frequent asymptomatic infections precluding in early diagnosis and treatment making clinical presentation of sequelae often the first indication of infection. Development of a safe, efficacious and affordable vaccine holds promise for the global spread of Chlamydia genital infections. Previously we have shown that intramuscular(IM) vaccination of Vibrio cholerae ghosts (VCG) expressing Porin B and PmpD showed protection of mice against intravaginal infections via the development of a cellular ( Th1) as well as humoral ( IgG2a and IgA) immunity. The present study was undertaken to examine the potential of rectal immunization for the induction of genital tract immunity against heterologous Chlamydia infection in mice. The impact of immunization with the VCG vaccine in combination with Flt3 Ligand (FL) on induction of immunity was also investigated. The results demonstrate that both IM and IR rVCG immunizations elicited high levels of antigen-specific Th1 cell-mediated and humoral immune responses that were enhanced following co-immunization with FL. Also, rectally immunized mice were significantly protected against heterologous infection with serovar E Chlamydia 2 weeks post immunization. These results highlight the potential of rectal immunization for eliciting immunity in the female genital tract against Chlamydia and other sexually transmitted diseases.
Phenotypic and functional evaluation of T cell responses after intradermal immunization with LTR192G, an attenuated form of the enterotoxigenic E. coli (ETEC) labile toxin (LT), as an adjuvant for an ETEC vaccine (VAC8P.1004)
Authors: Laird Renee , Gutierrez Ramiro , Savarino Stephen , Riddle Mark , Maciel Milton 
Published: January 2023

Abstract
The skin is an appealing route for delivery of vaccines. It is easily accessible, is rich in antigen presenting cells (i.e. dendritic cells), and several reports have shown that intradermal (ID) vaccination can use less antigen (dose sparing). However, few new adjuvants have been developed and tested for skin immunization. Here, we report our findings on the evaluation of the T cell response after immunization of volunteers with two prototype vaccines against ETEC given ID with LTR192G. Volunteers were immunized on days 0, 21 and 42 with the tip adhesin of the class 5a CFA/I fimbriae, CfaE, or an adhesin-toxoid chimera protein, CfaE-sCTA2/LTB5, admixed with the adjuvant. We found marked activation of LTB- and CfaE-specific CD4+ T cells post-immunization as measured by CD69 upregulation. Within the LTB-specific CD4+ population, we found a greater frequency of skin-homing CCR4+ cells, which is consistent with the route of immunization and a strong response to LTR192G. In addition, there was a higher frequency of LTB-specific CD4+ T cells with an effector memory phenotype. The frequency of CfaE-specific IFNγ+ CD4+ T cells was significantly higher post-immunization and was validated by high levels of IFNγ in CfaE-stimulated supernatants. Cytokine analysis also revealed higher levels of CfaE-specific IL-6 secretion compared to LTB. Taken together, the data demonstrate a strong CD4+ T cell response was generated to both antigen and adjuvant after ID immunization.
Inclusion of flagellin increases antibody responses in nonhuman primate neonates following influenza vaccination (VAC8P.1002)
Authors: Kim Jongrok , Holbrook Beth , Hayward Sarah , Blevins Lance , Alexander-Miller Martha 
Published: January 2023

Abstract
Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response to vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for use in this vulnerable population. To address this issue we developed an African Green Monkey model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a TLR5 agonist, to serve as an effective adjuvant for vaccination of neonates. Animals were primed and boosted with inactivated PR8 influenza virus in the presence of either flagellin or an inactive form of the protein. Inclusion of flagellin significantly increased the level of influenza-specific serum IgG present following boosting as well as at early times after virus challenge. Animals receiving flagellin adjuvanted vaccination also exhibited higher levels of respiratory influenza-specific IgG at early times post challenge. Interestingly, there was no flagellin mediated increase in IgM. The presence of flagellin also resulted in an increase in neutralizing antibody. This study supports further exploration of flagellin as an effective adjuvant for inducing vaccine responses against influenza in neonates.
Sepsis increases susceptibility to chronic infection and exacerbates CD8 T cell exhaustion (VIR4P.1008)
Authors: Condotta Stephanie , Rai Deepa , Griffith Thomas , Badovinac Vladimir 
Published: January 2023

Abstract
Sepsis survivors often display impairment in innate and adaptive immune responses and become highly susceptible to ‘secondary’ infections with intracellular pathogens that are normally controlled by CD8 T cells. It is unknown if or when this observed immunoparalysis of CD8 T cell immunity recovers, and the long-term consequences of sepsis on the ability of naïve CD8 T cells to respond to subsequent infections are poorly understood. Previously, we demonstrated that sepsis has sustained detrimental effects on the capacity of CD8 T cells to respond to acute viral and bacterial infections. Here, using the cecal ligation and puncture (CLP) mouse model, we show that mice recovering from a septic event are more susceptible to chronic LCMV Clone-13 infection demonstrated by increased morbidity and mortality. LCMV-specific CD8 T cells from chronically infected CLP mice display an increase in inhibitory molecule expression (e.g., PD-1) and diminished Ag-driven cytokine production, suggesting that sepsis exacerbates CD8 T cell exhaustion following chronic viral infection. Furthermore, this exhausted phenotype of virus-specific CD8 T cells is observed earlier in LCMV Clone-13 infected septic mice compared to control mice. Together, these results illustrate that sepsis increases the vulnerability to chronic infections and can result in substantial and long-lasting changes in the CD8 T cell compartment affecting the ability of the host to respond to newly introduced antigens.
Systemic hematogenous maintenance of memory inflation by MCMV infection (VIR4P.1013)
Authors: Smith Corinne , Turula Holly , Snyder Christopher 
Published: January 2023

Abstract
Cytomegalovirus (CMV) is a β-herpesvirus that establishes a latent infection and supports the life-long maintenance of very large numbers of virus-specific effector T cells. These T cells remain functional and are found in many organs in the body. Current models propose that, to sustain these populations, reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and differentiation, followed by migration of progeny to non-lymphoid tissues. We tested this model using murine CMV (MCMV). While MCMV transcriptional activity during latency was below our limit of detection, proliferation of MCMV-specific effector T cells was antigen-dependent and was used as a read-out for antigen encounter. As shown previously, T cells within draining lymph nodes divided at a higher rate than cells elsewhere. However, pulse-chase experiments with BrdU failed to reveal migration of recently divided T cells from lymphoid to non-lymphoid tissues. In fact, inflationary cells observed in non-lymphoid organs were primarily perfusion-resistant cells residing in the vasculature. Strikingly, inhibition of T cell egress from lymph nodes did not eliminate T cell division in circulation, and did not prevent the maintenance of the circulating inflationary population during long-term treatment. Together these results suggest that memory inflation in response to MCMV is driven by viral antigen presented by cells that are accessible to the blood supply.
Mouse cytomegalovirus glycoprotein m153 binds a dendritic cell-surface ligand (VIR5P.1026)
Authors: Tilahun Mulualem , Revilleza Maria Jamela , Mans Janet , Natarajan Kannan , Margulies David 
Published: January 2023

Abstract
Mouse cytomegalovirus (MCMV) is a valuable model for studying virus-host interactions and mechanisms of viral immune evasion. MCMV encodes the m145 family of glycoproteins with predicted MHC-I structure. Among these, m153 is expressed on the surface of infected cells predominantly during the early phases of infection, independent of β2 microglobulin and peptide. We previously determined the X-ray structure of m153, establishing that it has an MHC-I-like fold and forms a stable non-covalent dimer. To identify immune cells that might express a ligand for m153, we constructed a reporter cell in which the extracellular domains of m153 were linked to human ζ chain driving green fluorescent protein upon activation. Using the reporter cell assay, we observed that CD11c+ splenic dendritic cells (DCs) and bone marrow DCs potently stimulate the m153 reporter cell. Further characterization of these cells by flow cytometry staining with an m153 tetramer and a battery of DC markers, as well as antibody blocking experiments, suggested several candidates for the m153 ligand. Transfectant cells and gene knockout animals are being studied to confirm the identity of these candidates. The identification of a host cell ligand for m153 should improve our understanding of mechanisms of host immune suppression during viral infection and will provide insight on the evolution of viral immune evasion.
In vivo silencing of microRNA-155 (miR-155) ameliorated pulmonary hemorrhage induced by pristane (BA12P.100) (BA12P.100)
Authors: Zhou Shiyu , Liang Dong , Huang Xinfang , Harley John , Shen Nan 
Published: January 2023

Abstract
Background: MiR-155 is a typical pleiotropic miRNA that participates in various aspects of immunity. In this study, we systemically examined the role of miR-155 in the development of pulmonary hemorrhage (PH) in Pristane-induced lupus. Methods: Mice received a single i.p injection of 0.5 ml Pristane. 2 weeks later, lung tissues were collected for pathologic assessment. Total lung RNAs were assayed by qPCR or subjected to gene profiling. Gene profiling data was analyzed by IPA software. Serum cytokines were messured by Bio-plex Assays. Results: We showed that miR-155 was elevated in lung tissues after Pristane treatment. MiR-155 KO mice appeared to develop attenuated PH, with reduced levels of pro-inflammatory cytokines (TNF-a, IL-6). By integrating the gene expression profiling data from miR-155 KO mice with microRNA target predication, our data suggest that PPARα, an anti-inflammatory transcription factor, is a novel functional target of miR-155. Furthermore, we showed that in vivo silencing of miR-155 by miR-155 antagomir significantly ameliorated PH induced by Pristane. Consistently, the pro-inflammatory cytokines (TNF-a, IL-6) were reduced upon miR-155 silencing. Conclusion: Overall, our study shows that knockdown of miR-155 by miR-155 antagomir inhibits Pristane induced PH through reducing the production of pro-inflammatory cytokines. This finding suggests a promising therapeutic potential of miR-155 antagonist in the treatment of acute lung inflammation in lupus.
Role of OX40/OX40L signaling in the expansion of regulatory T cells in the NOD mouse model (BA13P.127)
Authors: Haddad Christine , Bhattacharya Palash , Prabhakar Bellur 
Published: January 2023

Abstract
Type 1 diabetes (T1D) is a T-cell-mediated disease characterized by destruction of pancreatic beta cells. Unfortunately, most treatment options for T1D are non-specific, with many side effects. Regulatory cells T (Tregs) play a crucial role in the maintenance of immune homeostasis against self-antigen. Many studies have revealed that Tregs in patients with various autoimmune diseases, including T1D, are diminished in number and/or dysfunctional. The therapeutic potential of Tregs has not been fully understood because generating large numbers of Tregs has remained a challenge. Recently, we reported that bone marrow precursor cells differentiated with GM-CSF (BMDCs) are able to selectively expand Tregs ex-vivo. Further investigation revealed that this expansion is TCR-independent but requires OX40/OX40L interaction. Thus, here we wanted to study whether treatment with soluble OX40L can expand Tregs in-vivo and in the NOD mice. Surprisingly, treatment with OX40L caused rapid onset of T1D in 12 wk but not 6 wk old mice. Analysis of spleens and lymph nodes showed an increase in Tregs only in the 6 wk old OX40L group. Thymic analysis revealed an increase in Tregs in both the 6 and 12 wk old OX40L groups. Interestingly, OX40L specifically induced the stable Tregs subset in 6 wk old mice, but the labile Treg subset in the 12 wk old mice. Based on these findings, we propose that OX40L can specifically induce different subsets of Tregs based on the cytokine milieu.