bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant human IL‐7 (rhIL‐7) preferentially expands CD4+ and CD8+ naïve T cells and enhances T cell receptor (TCR) repertoire diversity
Authors: Sportes Claude , Hakim Frances T , Memon Sarfraz A , Zhang Hua , Brown Margaret R , Fleisher Thomas A , Krumlauf Michael C , Babb Rebecca R , Chow Catherine K , Fry Terry J , Engels Julie , Buffet Renaud , Morre Michel , Venzon David J , Korngold Robert , Pecora Andrew , Mackall Crystal L , Gress Ronald E 
Published: June 2021

Aging is associated with a decline in T cell generation and TCR repertoire diversity and a progressive accumulation of oligoclonal, terminally differentiated and functionally limited CD8+ effector T cells which may impede new responses. A phase I study of rhIL‐7 (subcutaneously every other day for 2 weeks) evaluated toxicity and biologic activity in 16 adults (age 20–71). RhIL‐7 was well tolerated. It resulted in a dose but not age dependent preferential expansion of naïve CD8+ T cells and of CD4+ RTEs, naïve and central memory T cells. (4 to 5‐fold at the higher doses of 30 and 60 μg/Kg/dose). T cells remained functional in vitro and persisted for 6–8 weeks. The naïve T cell expansions resulted in increased TCR diversity assessed before and one week after treatment. We scored divergence between each Vβ spectratype and normal standard comparing all the pre and post scores by Wilcoxon paired test. The increase in diversity was statistically significant in 4 of 6 subjects in CD4+, CD8+ or both.RhIL‐7 resulted in circulating T‐cell profiles resembling what is seen early in life with abundant naïve T‐cells and wide TCR diversity. We propose that rhIL‐7 has the potential of becoming a clinically usable T‐cell growth factor for rejuvenation of peripheral T‐cell populations in hosts with impaired immunity due to physiologic (age), iatrogenic (chemotherapy) or pathologic (HIV) lymphodepletion.
Expression of TNF‐α, IFN‐γ, TGF‐β and IL‐7 on cells isolated from the Bronchoalveolar Fluid in a model of secondary immunodeficiency.
Authors: Luczak Erica Natalia , Calabrese Graciela Cristina , Roux Maria Estela 
Published: June 2021

We have previously reported the early appearance (4 days post partum) of γδT cells that colocalize with TNF‐α in Bronchus‐Associated Lymphoid Tissue (BALT), indicating the important role of this cytokine for BALT development. In our experimental model of secondary immunodeficiency due to severe protein deprivation at weaning followed by administration of a 20% casein diet during 21 days (R21), we also demonstrated an increase of TCR γδ+ cells accompanied by an increase in TNF‐α+ cells number in R21. The objective of this work is to analyze and compare cells isolated from the bronchoalveolar fluid (BAL) in R21 vs control rats: 1) the expression of TNF‐α and IFN‐γ, as indicator of an inflammatory process and its regulation by TGF‐β and 2) the cellular regulation by IL‐7. Western Blot analysis showed an increase of all cytokines in cells from BAL of R21 animals when compared to control rats (Figure 1). Our results indicate the existence of an inflammatory process (due to TNF‐α and IFN‐γ) modulated by TGF‐β. The increment of IL‐7 correlates with its capacity for the proliferation and differentiation of γδ T cells, which are increased in BAL from R21 as previously reported. Moreover, we suggest a protective role of IL‐7 in the inflammatory focus.Supported by B010 grant.
Interferon gamma selectively protects the cerebellum and brain stem from inflammation during EAE pathogenesis
Authors: Lees Jason R , Golumbek Paul T , Sim Julia , Russell John H 
Published: June 2021

In multiple sclerosis (MS) the localization of inflammatory foci within the central nervous system (CNS) is associated with prognosis, with lesions of the cerebellum correlated to a severe clinical outcome. Previous studies of experimental autoimmune encephalomyelitis (EAE), a model of MS, revealed distinct clinical outcomes correlated with the capacity to produce IFN‐γ. Outcomes were linked to localization of inflammatory cells in either the spinal cord (wild type (WT)) or the cerebellum and brain stem (IFN‐γ deficient).We demonstrate using an adoptive transfer system that the ability of the host to respond to IFN‐γduring EAE initiation determines the site(s) of CNS pathogenesis. Transfer of WT Th1 cells into IFNγR deficient mice results in invasion of the brain stem and cerebellum with attendant clinical symptoms, identical to the pathogenesis observed following transfer of IFN‐γ deficient T‐cells to WT hosts. Inflammation of the spinal cord associated with EAE in WT mice is abrogated in both IFN‐γdeficient models. These data demonstrate that interaction between cytokine(s) and host cells during the initiation of EAE determines localization of neuroinflammation. Further, these data reveal that IFN‐γ signaling can selectively protect CNS regions from T‐cell pathogenesis.Supported by a National Multiple Sclerosis Society Fellowship, NMSS research grants RG3314, RG 3732, and NIH grant # 5 T32 NS07205‐22.
Effect of genetic A2B adenosine receptor ablation on proinflammatory actions of adenosine in mast cells
Authors: Ryzhov Sergey , Zaynagetdinov Rinat , Goldstein Anna E. , Biaggioni Italo , Feoktistov Igor 
Published: June 2021

We have previously shown that A2B adenosine receptors (AR) play a pro‐inflammatory/pro‐angiogenic role, upregulating production of Th2 cytokines and angiogenic factors in human HMC‐1 mast cells.1,2 However, the pro‐inflammatory role of A2bAR in mast cells was recently questioned by a study that found an enhanced antigen‐induced degranulation of A2bAR knockout (A2BKO) mouse bone marrow‐derived mast cells (BMMCs).3 The authors interpreted this as evidence of anti‐inflammatory actions of A2BAR in BMMCs and suggested that A2BAR antagonists with inverse agonist activity could promote activation of mast cells. Here, we revisited these conclusions by studying the effect of genetic A2BAR ablation on adenosine‐dependent regulation of BMMCs. Our results show that genetic ablation of A2BAR had no effect on adenosine‐dependent potentiation of antigen‐induced degranulation, but abrogated adenosine‐dependent stimulation of IL‐13 and VEGF secretion. A2BAR antagonists with inverse agonist activity inhibited A2BAR‐dependent secretion, but did not mimic the enhanced antigen‐induced degranulation observed in A2BKO BMMCs. Thus, our study confirmed the pro‐inflammatory role of mast cell A2BAR and demonstrated anti‐inflammatory actions of A2BAR antagonists.Supported by NIH.
STAT3 phosphorylation induced by vascular endothelial growth factor is associated with regulation of immune responses by dendritic cells
Authors: Zhang Wenguang , Hauke Ralph 
Published: June 2021

OBJECTSThe expression of phosphorylated signal tranducer and activators of transcription 3 (p‐STAT3) is correlated with expressions of vascular endothelial growth factor (VEGF) in some carcinomas. The mechanism of the immunomodulatory effects of VEGF on human dendritic cells (DCs) is not clearly understood. This study seeks to investigate the effects of VEGF on STAT3 phosphorylation and its correlation with immune regulation by human DCs.METHODS: Monocytes‐derived immature DCs were incubated with VEGF. We detected expression of p‐STAT3 in DCs induced by VEGF with different concentrations and for different effect times by immunohistochemistry and Western blot. The cytotoxicity of DC‐activated T cells against LNCaP prostate cancer cells was determined by lactate dehydrogenase (LDH) activity assay.RESULTS: A concentration of 100 ng/ml of VEGF was enough to increase phosphorylation of STAT3 and showed nuclear translocation of p‐STAT3 from the cytoplasm to the nucleus. The cytotoxicity of T cells was significantly decreased after co‐culture with VEGF‐treated DCs.CONCLUSIONS: VEGF plays a key role in immunoregulation of human DCs. VEGF‐induced phosphorylation and nuclear translocation of STAT3 is correlated with DCs activation decreased, suggesting that VEGF decreased DC‐activated T cells cytotoxity activation by phosphorylation of STAT3. Supported by: UNMC Internal Medicine Research Support.
CD40 Ligation Enhanced Naïve Tumor Antigen Specific CD8+T Cell Responses in Spontaneous Osteosarcoma Model
Authors: Tagaram Hephzibah Rani S. , Rolin Oliver , Avella Diego , Garcia Luis , Kimchi Eric , Schell Todd , Tevethia Satvir S. , O‐Carroll Kevin F. Staveley 
Published: June 2021

Introduction: The 501 transgenic mice express the transforming T antigen (Tag) of SV40 virus causing spontaneous Tag expression in bone and salivary gland of mice. T ag expression as a self‐antigen in osteosarcoma mice leads to progressive loss of CTL responses to T ag epitopes.Objective: 1.To determine the fate of naïve TCR‐I cells in tumor bearing osteosarcoma mice that express T antigen as a tumor antigen. 2. The effect of CD40 ligation on the above response.Experiment: T antigen epitope I‐specific CD8+ T cells from Tcell receptor transgenic mice (TCR‐I cells) were transferred into tumor‐bearing 501mice or syngeneic normal C57BL/6 mice. Agonistic anti‐CD40 was given day before and day after adoptive transfer(AT), seven days later spleens and cervical lymphnodes, tumors and salivary glands were analyzed for Interferon‐γ, epitope‐1 specific tetramer, T cell infiltration, and apoptotic TUNEL staining.Results: 1) TCR‐I cells expand systemically and acquire effector function 2) Tumor specific CD8+T cell responses are aepitope‐I specific. 3) CD40 ligation enhanced TCR‐I cell proliferate. 4) In tumor‐bearing hosts TCR‐I cells proved capable of lysing 100% of target cells in vivo. 5) TCR‐I cells infiltrates salivary gland and tumor and enhanced with CD40 ligation. 6) CD40 ligation enhanced anti tumor activity detected by apoptosis using TUNEL.Conclusion: T ag expressed as a tumor antigen in osteosarcomas mice is strongly immunogenic. CD40 ligation enhanced responses to T‐ag as measured by TCR‐I proliferation, activation, migration into tumors and antitumor cell cytotoxicity.
HLA‐B‐Associated Transcript 3 (BAT3), a ligand for Nkp30 is secreted from cells as Exosomes and enhances the activity of Natural Killer cells
Authors: Simhadri Venkateswara Rao , Reiners Katrin S , Hansen Hinrich P , Engert Andreas , von Strandmann Elke Pogge 
Published: June 2021

Natural Killer (NK) cells, defined as innate lymphocytes also serve as regulators of adaptive immunity via cytokine secretion and cross‐talk with dendritic cells (DCs). Both killing and maturation of DCs by NK cells is dependent on NKp30, a Natural Cytotoxicity Receptor (NCR) expressed on NK cells. However, the NKp30 specific cellular ligands have remained elusive.Recently BAT3 was identified as the tumor associated ligand for NKp30 (Immunity, 2007 in press). It is a nuclear protein characterized by a conserved BAG domain (BclBcl‐2 associated anthogene), that interacts with Hsp70.This abstract describes that BAT3 is secreted into the extracellular environment in exosomal fractions upon exposure to stress signals. The exosomes from the tumor cells and iDCs possess BAT3 on the surface. These exosomes activate NK cells and stimulate the cytokine release TNFalpha and IFNgamma. This release was enhanced by exosomes from cells overexpressing BAT3 and was inhibited by depleting the overexpressed BAT3. Moreover, the exosomes’ stimulation was inhibited when the cells were targeted with siRNA of BAT3.Thus we postulate that BAT3, a novel cellular ligand for NKp30 receptor has a role in the reciprocal activation of NK‐DC cross‐talk. We present evidence that BAT3 is secreted into exosomes, a novel group of immune regulators “Nucleokines”.Research was supported by Deutsche Forschungsgemeinschaft (DFG) (STR 530/5‐1).
Lewis Lung Carcinoma (LLC) alters the phenotype of murine lung mast cells resulting in a phenotype consistent with myeloid‐derived suppressor cells (MDSCs)
Authors: Mailloux Adam William , Young M Rita I 
Published: June 2021

MDSCs are among the most potent immune suppressive phenotypes found in the tumor microenvironment. Because they share so many characteristics with myeloid progenitors, MDSCs are thought to arise as a product of tumor‐associated hematopoiesis. However, a clear MDSC progenitor has yet to be identified. We used flow cytometry to demonstrate a significant increase in CD11b+ infiltrate in a murine model of LLC as compared to normal lung tissue. A large portion of this infiltrate also expresses the granulocyte/myeloid marker Gr‐1. Interestingly, CD11b+/Gr‐1+ cells in normal lung tissue also express the high affinity IgE receptor FcεR1α, which is indicative of mast cells. However, this FcεR1α expression is lost on these cells in LLC‐bearing animals in a tumor burden‐dependant manner. Additionally, conventional methylene blue stains show highly granulated mast cells in normal lung tissue while showing a complete lack of granulated cells in LLC‐bearing lung tissue. We also immunomagnetically isolated Gr‐1+ mast cells out of normal lung tissue and incubated them in‐vitro with LLC‐conditioned media while monitoring their FcεR1α expression, granularity, and morphology in an attempt to reproduce the phenotypic changes seen in‐vivo. Our data suggests that in LLC, MDSCs may originate from fully differentiated mast cells rather than from myeloid precursors.Supported by the Dept of Veteran's Affairs & NIH
Substance P modulation of anti‐tumor immunity in a mouse model: characterization of NK and T cells
Authors: Brand Lucas , Kastelic Amanda , Spampinato Christine , Manske Jill 
Published: June 2021

Substance P (SP) is a neuropeptide that has been shown to have immunoregulatory properties including effects on mediators involved in anti‐tumor immunity. In previous studies we have shown that treatment of mice with SP provides protection against tumor growth. This protection requires both T cells and NK cells, and adoptive transfer cells from SP‐treated animals can transfer tumor protection. In this study we characterized NK and T cells from SP treated mice. Mice were implanted with osmotic pumps that delivered SP for 5, 9, or 14 days. Following treatment, we examined the expression of the CD25 as a marker of T cell activation, and CD69 expression on NK cells. NK cells from SP‐treated mice showed up regulation of CD69. No SP effect was observed on CD25 expression. To further characterize the T cells involved in this response, we examined the effect of SP on proinflammatory cytokines. Levels of intracellular Interleukin‐2 (IL2), gamma‐Interferon (IFNγ), and Tumor Necrosis Factor (TNFα) were examined. SP treated mice had increased levels of IFNγ after five days of SP treatment, even in the absence of additional in vitro stimulation. These results suggest that the role of T cells in SP mediated tumor protection may be via production and release of proinflammatory cytokines which may, in turn, affect activation of NK cells.This work was funded in part by a Young Scholars grant from the University of St. Thomas
Characterization of The Bovine Mammary Serotonergic System
Authors: Hernandez Laura Lorraine , Limesand Sean W. , Baumgard Lance H , Horseman Nelson D , Collier Robert J 
Published: June 2021

Previous research indicates serotonin (5‐HT) as a feedback inhibitor of lactation in the bovine. We utilized quantitative real‐time PCR (qRT‐PCR) and in situ hybridization of tissue cryosections to identify 5‐HT receptors in bovine brain (BB), mammary tissue (BMT) and primary bovine mammary epithelial cells (BMEC). Additionally, we utilized immunohistochemistry in BB and BMT cryosections to determine presence of tryptophan hydroxlase 1 (TPH‐1), aromatic amino acid decarboxylase (AADC), and the serotonin reuptake transporter (5HTT). Serotonin receptors 1b, 2a, 2b, 4, and 7 were detected in the BB, BMT and BMEC by PCR and qRT‐PCR. In BMT, fold expression of receptors relative to BB, (highest to lowest) was: 5‐HT 1b (2,477; P < 0.0001), 5‐HT 4 (389), 5‐HT 2b (89), 5‐HT 7 (18), and 5‐HT 2a (3.77). In BMEC, the fold expression of receptors relative to BB (highest to lowest) was: 5‐HT 4 (230, P < 0.0001), 5‐HT 2b (44), 5‐HT 7 (37), 5‐HT 1b (30) and 2a (1.64). Serotonin receptors 1a, 1d, 1f, and 2c were only detected in the BB by PCR. Immunostains for TPH‐1, AADC, and 5HTT were positive in both BB and BMT. We conclude that BMT and BMT enriched with BMEC contain the 5‐HT 1b, 2a, 2b, 4 and 7 receptors. The enrichment of tissue preparation with BMEC had the highest expression of the 5‐HT 4 receptors relative to BMT, while BMT had the highest expression of 5‐HT 1b receptors relative to BMEC. Manipulation of 5‐HT receptors with specific antagonists present in BMEC could lead to increased milk protein synthesis.*Funded by USDA‐NRI#2007‐35206‐17898
Breastfeeding as a predictor of body mass index in 2‐year‐old children at risk for overweight
Authors: Street Erin E , Lovelady Cheryl , Ostbye Truls , Pendzich Margaret , Fuemmeler Bernard 
Published: June 2021

The purpose of this study was to determine if breastfeeding was associated with BMI of children at 2 yrs who were at risk for obesity. Overweight/obese mothers (BMI = 32.9 ± 7.3 kg/m2) and their children were studied from 7 wks until 2 yrs postpartum (PP). Baseline data included race, education, income, age, marital status, gestational wt gain, and birth wt. At 1 yr PP mothers reported infant feeding. Women were assigned 0 if formula feeding only, 1 if combining formula and breastfeeding, and 2 if breastfeeding only for each month during the first year PP. A lactation score was calculated by totaling the values for each month. Scores were used to define two groups: 1) low intensity/duration (score=0–11, N=129) and 2) high intensity/duration (score=12–24, N=74). Race was 51% white, 46% African American and 3% other. At 2 yrs PP, 20% of children were overweight and 24% were obese using WHO growth standards. Multiple regression analysis was used to determine predictors of child BMI at 2 yrs. Variables were baseline data, gender, mothers BMI and breastfeeding group. The model accounted for 16% (p<0.001) of the variation in child BMI. Birth wt (p=0.01), mother BMI (p=0.03), and gestational wt gain (p=0.06) predicted an increase, while high intensity and long duration of breastfeeding (p=0.07) predicted a decrease in child BMI at 2 yrs. These results suggest breastfeeding may reduce obesity in children born to overweight/obese women.Supported by R01‐DK064986
Quality aspects in the determination of sodium in bread
Authors: Castanheira Isabel , Coelho Ines , Santiago Susana , André Catarina , Silva Ana Sanches 
Published: June 2021

Objective: In this work was studied the impact of sampling plan measurement uncertainty and appropriate reference materials in the determination of assigned value of sodium content in several bread types consumed in Portugal.Methods: The sampling plan was designed according to the national food balance sheets. Sodium was determined by flame photometry and measurement uncertainty was estimated in accordance with NIST guide.Results: The highest sodium value determined was 650 mg/100 g. Relative measurement uncertainty reaches in some cases 10%, where the largest contribution comes from sampling. In all types of bread analysed, the sodium values are significantly different between bakeries under study (p<0.001).Conclusions: Our study reveals that measurement uncertainty and the use of appropriated reference materials facilitates the evaluation of sodium content available in different bakeries. Sampling plan incorporated in quality assurance programme is a key criteria for extrapolate analytical into intake values and reduce the additional imprecision in nutrient intake estimation. The quality framework of sodium content in Portuguese bread can be applied in other countries across and beyond Europe.This work was completed on behalf of Project LMARSA and funded under the Regional Programme for European Cohesion.
Anemia and Decline of CD4 Cell Count in HIV+ Drug Users in Miami
Authors: Sales Sabrina , Campa Adriana , Rafie Carlin , Le Katherine , Entengoff Kirstin , Page John B , Baum Marianna K 
Published: June 2021

Objective:This study investigates the association of anemia with HIV disease progression and survival over 30 months in HIV+ drug users in Miami.Methods:After obtaining consent, demographic and medical questionnaires were completed every 6 months for 30 months in HIV+ drug users. Blood was drawn for CD4 cell count, viral load, and CBC. Anemia was defined as hemoglobin <12g/dL in women and <14g/dL in men, and hematocrit<37% in women and <42% in men. Kaplan Meier Estimation was used to evaluate the rate of decline of CD4 cell count and mortality over 30 months.Results:Of 231 participants, 77% were black, and 73% were men. Mean age was 42 years ± 7.1. The prevalence of anemia was 46% (n=106). Of those with anemia, only 19% had macrocytic/normochromic anemia and 0.05% microcytic/hypochromic anemia, suggesting nutritional deficiency. Anemia was significantly associated with a more rapid decline of CD4 cell count to below 200 cells/μL (p<0.001) when compared to participants without anemia. There was also a trend in decreased survival overtime in those who had anemia compared to those without anemia, (80% vs. 94%, p=0.094).Conclusions:Nutritional etiologies of anemia do not seem to be the predominant cause of anemia in this cohort. Anemia in our cohort was strongly related to advanced HIV disease and efforts to identify the cause and provide treatment may help to delay disease progression.Funded by NIDA
A comparison of hyperimmune egg protein and placebo for efficacy and safety among healthy young adults
Authors: Scheett Timothy P , Martin Tyler D. , Carr Benjamin M. , Koster Carolyn A. , Celmer Patricia A. , Whitener Jeffrey A. , Webster Michael J. 
Published: June 2021

To evaluate the safety and efficacy of oral HIE supplementation during a sample training program. Twenty‐four recreationally active males (23.6 yrs, 176 cm, 69.2 kg and 17.1 % body fat) were randomly assigned to either HIE (n=12) or an egg protein placebo (PLA) group. Participants were supplemented with 4.5 g/d for 2 d, 9 g/d for 2 d and 13.5 g/d for 6 d. HIE and PLA supplements were identical in appearance and taste before and after mixing with 237 mL of milk. Subjects recorded duration and severity of adverse events in a daily log. HIE and PLA had a 100% compliance with the study protocol. 17% (n=2) of HIE and 25% (n=3) of PLA reported experiencing at least one adverse event. HIE reported experiencing adverse events for a total of 10 d as compared to 24 d for PLA. In HIE one subject reported experiencing stomach ache and diarrhea for 3 d (severity of 2 on a 10 pt scale) and another subject reported a skin rash lasting 4 d (severity of 6). In PLA one subject reported experiencing stomach ache and vomiting for 3 d and increased thirst and feeling tired/sleepy for 3 d (severity of 7 and 8, respectively). Subjects reported a runny nose (n=3) lasting 1–3 days (1–5 severity) and a cough (n=2) lasting 3 d (severity 1–5). HIE was associated with fewer adverse events of similar or lesser severity than PLA and all adverse events were minimal and transitory in nature with none requiring medical intervention.Supported by Legacy for Life, LLC, Melbourne, FL