bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential immune responses to seasonal IM flu-vaccines (113.36)
Authors: Kasten-Jolly Jane , Lawrence David 
Published: January 2023

Abstract
T (total, CD4 and CD8), B, and NK lymphocytes were enumerated by flow cytometry (4-color MultiTest) before and after intramuscular injection of the 2005/2006, 2006/2007, 2007/2008, 2009/2010, and 2010/2011 vaccines as an initial step in the characterization of the immune response to vaccine preparations. Study subjects (yrs 2005-2007) ranged in age from 25-68 yrs, while the 2009/2010 flu-shot subjects were 59-80yrs with one 30yr young control. The first 3 seasons included 11 subjects common to all seasons and 8 others common to the 2006/2007 and 2007/2008 vaccination season. Blood lymphocyte numbers were assessed 5-7 days before, and 3-6 days and 12-14 days post-vaccination. The 2010/2011 study included 2 subjects from previous years and 1 (35 yr) new to the study. Most of the vaccines, except 2010/2011, which induced an increase of B cells and CD4 and CD8 T cells, induced no detectable increase in these lymphoid subsets; the 2006/2007 and 2007/2008 vaccines actually caused a decline in T cells at 2 wks post vaccination. However, the 2006/2007 vaccine did increase NK cell numbers at 5 days post vaccination, which returned to pre- numbers after 2 wks. An increase in B and T-cell numbers after the 2010/2011 vaccine was associated with the highest influenza virus-specific antibody titer. Since most of the individuals in these studies remained constant, the results indicate that different vaccine preparations affect the immune system in different ways.
Evaluation of HCMV vaccines in rhesus macaques by a novel micro-neutralization assay (113.4)
Authors: Tang Aimin , Li Fengsheng , Freed Daniel C. , He Xi , Finnefrock Adam , Casimiro Danilo , Wang Dai , Fu Tong-Ming 
Published: January 2023

Abstract
Human cytogemalovirus (HCMV) causes wide-spread infection in adult human populations. Although no symptoms observed in healthy persons, HCMV infection can cause severe and even life-threatening diseases in immune-compromised individuals. There are lines of evidence that humoral immunity can provide protection against HCMV infection. We have tested several versions of HCMV vaccines based on laboratory strain AD169 with its epithelial tropism restored in rhesus macaques. Vaccines were administered intramuscularly three times. In comparison, recombinant HCMV gB protein vaccine, which showed marginal protections in previous clinical trial, was given with adjuvant MF59. To facilitate the evaluation of these vaccines, we have developed a novel micro-neutralization assay based on the detection of a dominant HCMV antigen expressed in ARPE19 cells, using near infrared dye-labeled immune reagents, to measure HCMV neutralizing activities in serum samples of vaccinated monkeys. Our results showed that AD169 revertant vaccines induced much stronger neutralizing activities than recombinant gB vaccine in rhesus monkeys. The addition of ISCOMATRIX adjuvant (CSL, Ltd) in the vaccine formulation further enhanced its immunogenicity. There were significant boost effects after the second injection, while the third injection did not increase the neutralizing titers above those obtained post the second vaccination.
HSV-2 antigens formulated with Matrix M-2 induce balanced neutralizing antibody and durable polyfunctional T cell responses in mice (113.5)
Authors: Lee Alexander , Larson Shane , Zielinski Veronica , Long Deborah , Flechtner Jessica , Skoberne Mojca 
Published: January 2023

Abstract
An effective HSV-2 vaccine is still needed despite the prevalence of antiviral drugs. Recent HSV-2 vaccine clinical trials highlighted the need to elicit potent T cell responses since neutralizing antibodies alone were incapable of providing complete protection. Through proteomic screens using T cells of HSV-2-exposed donors several antigens were identified as promising vaccine targets. Two of these antigens, GB208 and GB217 (GEN-003), were formulated with a saponin-derived adjuvant Matrix M-2, which in recent avian influenza human clinical trials induced cellular and humoral immune responses. In preclinical studies, C57BL/6 mice were used to evaluate the ability of GEN-003 combined with Matrix M-2 to induce antigen-specific T cell and antibody responses. T cell effector functions were evaluated by IFNγ ELISPOT, intracellular cytokine staining, and in vivo cytolysis of fluorescently labeled peptide-pulsed targets. Neutralizing antibody responses as well as total and subclass IgG titers were also assessed. Cellular and humoral immune responses were primed in mice after administering a wide range of protein and adjuvant doses. GB208- and GB217- specific T cell responses were polyfunctional, cytolytic, and persisted for more than 3 months. Antibody responses were neutralizing, and represented balanced Th1/Th2 phenotypes. In conclusion, GEN-003 combined with Matrix M-2 form a promising vaccine candidate that activates both arms of the immune system necessary for viral clearance.
Impaired NLRP3 inflammasome activity in elderly hosts contributes to the prevalence of primary and secondary Streptococcus pneumoniae infection. (114.4)
Authors: Stout-Delgado Heather , Shirali Anushree , Jaramillo Richard , Harrod Kevin 
Published: January 2023

Abstract
Lethal pneumonia has become a serious problem in elderly populations. Although influenza infection alone may lead to pneumonia, secondary bacterial infections, such as Streptococcus pneumoniae, during and shortly after recovery from influenza infections are more common. Previous work has demonstrated that the NLRP3 inflammasome is activated in the lung during influenza viral infection by the M2 ion channel as well as during S. pneumoniae bacterial infection by pneumolysin; however, the impact of aging on inflammasome function during primary or secondary S. pneumoniae infection has not been examined. Here, we show that elderly mice infected with S. pneumoniae alone or shortly after influenza infection produced lower levels of IL-1β and IL-18 during infection when compared to young mice. Further, elderly mice had increased morbidity, decreased cellular infiltration to the lung, and higher bacterial titers in lung during both primary and secondary bacterial infections. Examination of whole lung tissue collected from elderly mice exhibited decreased expression of ASC, NLRP3, TXNIP, and capase-1, but similar expression of pro-IL-1β and pro-IL-18, when compared to young, similarly infected mice during both primary and secondary bacterial infections. Taken together, our study demonstrates that during primary and secondary S. pneumoniae infections, elderly mice have impaired NLRP3 inflammasome activity which may contribute to increased susceptibility for developing pneumonia.
IL-4 has a critical, mouse strain-limited role in innate memory CD8+ T cell development. (115.19)
Authors: Morris Suzanne , Heidorn Stephanie , Perkins Charles , Hildeman David , Finkelman Fred 
Published: January 2023

Abstract
Mice have large numbers of innate memory cells: CD8+ T cells that develop functional and phenotypic memory cell characteristics in the absence of purposeful immunization. The role of IL-4 production by iNKT cells in innate memory cell development is shown by an ~80% decrease in splenic memory phenotype CD8+ T cell number in IL-4-, IL-4Rα-, Stat6- and CD1d KO BALB/c mice and an ~1/3 normal basal IL-4 level in CD1d KOs. The stimulatory effect of IL-4 on innate memory cell development is first observed in CD8hiCD4lo thymocytes and persists through adulthood. Anti-IL-4 mAb decreases innate memory cell number in thymus and spleen in immature mice, but only in thymus in adults. In contrast to BALB/c mice, IL-4Rα deficiency has little effect on CD8+ memory phenotype T cell number in C57BL/6 mice. This BALB/c - C57BL/6 difference is not associated with appreciable differences in basal total body or thymic IL-4 expression, CD8+ T cell IL-4Rα expression or IL-4 responsiveness, but is associated with greater IL-15Rα and IL-2/15Rβ expression and IL-15 responsiveness by C57BL/6 than BALB/c CD8+ splenocytes. In 5 additional mouse strains studied, 3 resemble BALB/c and 2 resemble C57BL/6 mice with regard to the IL-4 stimulation of innate memory cell development; an IL-4 effect correlates positively with thymic memory phenotype CD8+ T cell number. Thus, IL-4 produced by thymic NKT cells has a major role in memory phenotype CD8+ T cell development that varies among mouse strains.
Enhanced cell cycle activation in response to stimulation in RGC-32-/- T lymphocytes (115.3)
Authors: Tegla Cosmin , Cudrici Cornelia , Nguyen Vinh , Khan Ali , Vlaicu Sonia , Rus Violeta , Badea Tudor , Rus Horea 
Published: January 2023

Abstract
We have previously identified Response Gene to Complement (RGC)-32 as a factor induced by complement activation, growth factors and cytokines. To study the in vivo function of RGC-32, we have generated mice carrying a null allele of the gene. Mice lacking RGC-32 were generated by replacing most of the second exon of the RGC-32 gene with sequences encoding neomycin resistance. These mice develop normally, have a similar size as wild type (WT) mice and a normal life span. Although RGC-32 was found to be involved in cell cycle regulation in vitro and is considered a tumor suppressor gene, RGC-32-/- mice do not spontaneously develop overt tumors. Little is known about the roles played by RGC-32 in T-cell proliferation. The effect of the lack of RGC-32 on cell cycle activation was investigated in CD4 cells isolated from spleen. Proliferation of anti-CD3/anti-CD28 stimulated CD4 cells from RGC-32-/- mice measured by [3H]-thymidine incorporation was significantly increased when compared with WT mice. In addition, by flow cytometry, both CD4 and CD8 T-cells from RGC-32-/- mice displayed a significant increase in the percentage of proliferating Ki-67 cells upon TCR stimulation. Furthermore, Akt phosphorylation was induced significantly in CD4 cells of RGC-32-/- when compared with WT mice. Our data indicate that in T-cells, RGC-32 plays an important role in inhibiting cell cycle activation by suppressing Akt activation.
The acute effects of sub-lethal gamma irradiation on the thymus and T cells were directly affected by age, sex and radiation exposure dose (115.8)
Authors: Xiao Shiyun , Zhang Wen , Manley Nancy 
Published: January 2023

Abstract
To study the effects of A-bomb radiation on immunosenescence, we developed a mouse model to evaluate the effects of sub-lethal gamma irradiation, varying exposure dose and analysis time points in males and females. The current data report the effects on 2 and 6-month old mice exposed at 0, 0.5, 1, 2, or 4 Gray (Gy), analyzed 1.5 months after irradiation. We saw a dose dependent reduction of DN1 thymocytes, especially of DN1a,b subsets. Although DN cells were reduced, the DP subset was increased, with a dose dependent restoration of total thymocyte numbers at all but the highest exposures. Significantly, there was a dose dependent increase of CD4 and decrease of CD8 SP cells, resulting in an increased CD4/CD8 ratio. Thymic NK cell numbers were increased at low doses, but decreased at the 4Gy dose. In males, total peripheral T cell numbers showed a dose-dependent decline while thymocyte numbers showed the opposite effect. In contrast, peripheral T cells showed the same increased CD4/CD8 ratio as thymocytes. Newly produced thymocytes contributed more to restoration of peripheral T cells at low doses, but peripheral homeostasis appeared to have more effect at 4Gy. Thymic epithelial cells (TECs) were also affected, with an increase of total TEC number at low doses followed by a dose dependent reduction at higher doses. These results suggest that age, sex and exposure dose all affect the restoration of the immune system during early recovery period after sub-lethal irradiation.
Tregitope applications to tolerance induction in autoimmune diseases. (116.10)
Authors: Cousens Leslie , De Groot Anne , Najafian Nader , Mingozzi Federico , Elyaman Wassim , McClaine Elizabeth , Mazer Bruce , Hui Daniel , Khoury Samia , Su Yan , Scott David , Martin William 
Published: January 2023

Abstract
Modulation of T cell responses may contribute to the design of new approaches for the treatment of autoimmune and inflammatory diseases. IVIG is one example of a therapy with this effect, and evidence is accumulating that Tregitopes (De Groot et al. Blood, 2008, 112:3303; natural T regulatory epitopes derived from IgG) provide beneficial immunomodulatory effects that parallel the effects of IVIG. In this presentation, we will provide evidence that Tregitope sequences derived from human IgG can reproduce immunomodulatory effects of IVIG in vitro and in vivo. In vitro, Tregitopes activate CD4+CD25+FoxP3+ natural regulatory T cells (nTreg). In vitro and in vivo, Tregitopes cause Tregs to produce IL-10, and to expand, and iTreg are induced. Induction and functions of nTregs have been examined in model systems such as D011.10 TCR transgenic mice, transplant of BM12 to C57BL/6, AAV-mediated gene transfer and EAE. Together, the data show that effector T cells, Th17, and Th9 cells are modified in the presence of Tregitopes. In OVA-induced allergic airway disease, we observed significant and reproducible expansion of Tregs in conjunction with decreased airway reactivity that was comparable to, if not greater than IVIG. We will provide additional unpublished evidence demonstrating the antigen specificity of tolerance induction using Tregitopes in conjunction with target antigens, and discuss the relevance of Tregitopes to the treatment of human immune-mediated diseases.
Immune regulatory mechanisms, not alteration in Th1/Th2 skewing, are responsible for helminth-mediated protection against type 1 diabetes in NOD mice. (116.3)
Authors: Mitre Edward , Shi Yinghui , Torrero Marina , Mueller Ellen , Larson David , Soloviova Katerina , Stocker J. , Davies Stephen , Tarbell Kristin , Hubner Marc 
Published: January 2023

Abstract
Both Th2 immune responses and regulatory responses are increased during helminth infection and have the potential to be the mechanisms by which helminth infections protect against Th1-driven autoimmune diseases. We investigated these mechanisms by evaluating diabetes development in NOD mice infected with the filarial nematode Litomosoides sigmodontis in settings of depletion or absence of IL-4, regulatory T cells, IL-10, and TGFβ. Despite the absence of a Th2 immune shift, infection of IL-4-deficient NOD mice with L. sigmodontis prevented diabetes onset in all mice studied. Infections in immunocompetent and IL-4-deficient NOD mice were accompanied by increases in CD4+CD25+FoxP3+ regulatory T cell frequencies and numbers, respectively, increased proliferation of CD4+FoxP3+ cells, and increased production of TGFβ. Depletion of FoxP3+ T cells from splenocytes transferred into NOD.scid mice did not decrease helminth-mediated protection against diabetes onset. Continuous depletion of the anti-inflammatory cytokine TGFβ, but not blockade of IL-10 signaling, prevented the beneficial effect of helminth infection on diabetes. This study demonstrates that helminth-mediated protection against autoimmunity is not dependent on the induction of a Th2 shift but does require TGFβ. These findings suggest it may be possible to develop helminth-derived therapies for autoimmunity that induce protective regulatory responses without upregulating potentially harmful proallergic Th2 responses.
Diurnal variations in the phagocytic activity of zebrafish kidney leukocytes can be influenced by melatonin in a time-of-day dependent manner. (117.13)
Authors: Hannum Lynn , Ruksznis Catarina , Storer Alex , Wright Travis 
Published: January 2023

Abstract
Diurnal variations in immune system function result from rhythmic expression of clock genes. Their relationship with neuroendocrine regulators such as melatonin is not well understood. We explored the influence of melatonin on variations of phagocytic activity of zebrafish leukocytes. The percentage of kidney myeloid cells that phagocytosed pHrodo-labeled E. coli varied substantially throughout the day. The greatest increase in activity was between 6 AM and 10 AM, spanning the daily dark-to-light transition, a time when endogenous melatonin levels are falling to their daytime low. To determine whether extending the perceived night by prolonging the presence of melatonin would reduce the peak participation in phagocytosis observed at 10 AM, fish were exposed to exogenous melatonin for two hours beyond the beginning of the daily light period. Treatment with melatonin resulted in significantly lower participation in phagocytosis, similar to the normal 6 AM (dark phase) levels. The opposite effect was observed when fish received melatonin later in the day, prior to the evening light-to-dark transition. Fish exposed to melatonin prior to assay at 6 PM (late day) displayed a significant increase in phagocytosis over control fish, with participation levels surpassing normal 10 PM (early dark phase) levels. At both times of day, pre-treatment with the melatonin receptor antagonist luzindole prevented the changes in phagocytosis associated with extended melatonin presence.
Monocyte-derived tumor necrosis factor-α is essential for the protective immune response against Listeria monocytogenes (117.21)
Authors: Shi Chao , Williams Cassandra , Ling Lilan , Leiner Ingrid , Pamer Eric 
Published: January 2023

Abstract
Ly6Chi monocytes provide immune defense against infections. After being recruited from the bone marrow to sites of infection, Ly6Chi monocytes are localized to the bacterial foci and prevent infection from disseminating. In this study, we demonstrate that the antimicrobial functions of monocytes are largely dependent on their expression of TNFα, a pro-inflammatory cytokine. Specific ablation of TNFα expression from Ly6Chi monocytes significantly increases the susceptibility to L. monocytogenes infection in mice. Adoptively transferred monocytes lacking TNFα fail to provide protection, whereas their wild type counterparts do. TNFα produced by monocytes is required for organizing the cellular structure at hepatic lesions of infection that contains bacterial proliferation. It acts on monocytes and induces apoptosis in the cells harboring bacteria at the center of the lesion. Our findings provide insights for the function of TNFα and mechanisms by which monocytes contribute to host defense.
A predominance of PMN-II and M2b monocytes in alcoholics (117.9)
Authors: Kobayashi Makiko , Asai Akira , Tsuda Yasuhiro , Nakamura Kiwamu , Okita Yamato , Higuchi Kazuhide , Suzuki Fujio 
Published: January 2023

Abstract
Alcoholics are well-known to be immunocompromised hosts, and are susceptible to various infections. To determine the properties of effector cells in host antibacterial innate immunities, in the present study the functions and subsets of neutrophils and monocytes in peripheral blood of alcoholics were characterized. It has been reported that IL-12(+) neutrophils (PMN-I) and IL-12(+)IL-10(-) monocytes (M1 monocytes) are major effector cells in antibacterial innate immunities, while CCL2(+) neutrophils (PMN-II) and IL-12(-)IL-10(+) monocytes (M2 monocytes) are inhibitory on the generation of antibacterial effector cells. Neutrophils and CD14(+) monocytes, isolated from 10 alcoholics by Ficoll-Hypaque/dextran sedimentations and magnetic beads, were adjusted to 1 x 106 cells/ml and stimulated with or without 0.0075% SAC for 18 hrs (neutrophils) or 48 hrs (monocytes). Culture fluids harvested were assayed for cytokines by ELISA. In the presence of SAC, CCL2 was produced by neutrophils from alcoholics, while IL-12 was not detected in culture fluids of these neutrophils. Healthy donor neutrophils stimulated with SAC produced IL-12 (but not IL-10). Also, IL-10 and CCL1 were produced by monocytes from alcoholics, while healthy donor monocytes produced IL-12 under the stimulation. CCL17 and CXCL13 were not produced by monocytes derived from alcoholics. These results indicate that alcoholics are carriers of PMN-II and M2b monocytes.
Radiation combined with thermal injury: induction of a radio-resistant immature myeloid cell. (118.10)
Authors: Mendoza April , Brickey Willie , Neely Crystal , Ting Jenny , Cairns Bruce , Maile Robert 
Published: January 2023

Abstract
Increasing sophistication of terrorist attacks and recent nuclear energy crises have amplified the interest in the immunobiology of radiation combined with burn injury (RCI). Burn is associated with immunosuppression and increased mortality with lower doses of ionizing radiation. We hypothesize that RCI results in reduction of immune cell populations with a decrease in serum cytokine levels. C57BL/6 female mice underwent either a 20% TBSA full thickness contact burn or sham procedure. One burn group and one sham group received a single whole body dose of 5 Gy gamma radiation. Spleens and burn draining lymph nodes (dLN) were harvested 3 and 14 days later. Flow cytometry was performed to identify adaptive and innate cells. Serum was analyzed by multiplex bead array assay. IL-1β (day3), MCP-1 and IP-10 (days 3 and 14) were significantly elevated in RCI mice when compared to all other groups. At day 14, splenic and dLN T-cells, B-cells and neutrophils were significantly decreased after irradiation and RCI when compared to sham and burn alone. In contrast, numbers and percentages of Gr.1+CD11b+ cells were significantly increased. We confirmed these were not myeloid-derived suppressor cells as they did not suppress T cell proliferation in vitro. These data suggest that while RCI depletes immune cells, there are specific cytokine alterations and induction of a population of immature myeloid-derived cells which may act as a potential target for immune countermeasures.
Gene Expression of Defensin is Greatly Upregulated in Neonatal Neutrophils Following Labor (118.11)
Authors: Lawrence Shelley , Pereira Anne , Jiang Kaiyu , Frank Mark , Jarvis James 
Published: January 2023

Abstract
This investigation documents the variability of gene expression between neonatal and adult neutrophils at rest and following stimulation with lipopolysaccharide. Our hypothesis is that distinct gene expression differences will be observed between neonatal and adult neutrophils at rest and following stimulation with LPS. Methods: Cord (9) and adult (12) blood samples were collected per routine procedures. Neutrophils were isolated and divided into 3 groups, which were seeded at 1 X 10 6 ml into multiwall plates and incubated with or without LPS 10 ng/µL (Invivogen) for 0, 45, and 90 minutes. RNA was isolated and gene expression differences determined via the Illumina platform at the Oklahoma Medical Research Foundation. Signal intensities from each probe were quantitated, adjusted for local background, and quantile normalized (Matlabs; Natwick, MA) to adjust the marginal distribution of each sample. Summary: Neonatal cord neutrophils were up-regulated in &gt; 75% of differentially expressed genes at each time point as compared to adults. This difference remained relatively unchanged prior to and following LPS stimulation. Furthermore, neonatal neutrophils demonstrated a 13-16 fold increase in the expression of defensins prior to and following LPS stimulation. Conclusion: Hierarchical clustering of gene expression results showed distinct differences between adult and cord neutrophils in unstimulated and stimulated states.