bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel subset of myeloid suppressor cells in pediatric cancer patients (66.9)
Authors: Zhang Hua , Galli Susana , Mackall Crystal 
Published: January 2023

Abstract
Human myeloid cells contain several phenotypically and functionally distinct subpopulations. Among these are myeloid derived suppressor cells (MDSC), which are identified as CD11b+Gr-1+ in mice, but are more heterogeneous in humans. A clear consensus does not exist regarding the phenotypic definition of human MDSC, but some have described them as CD33+CD11b+CD14- HLA DR- cells, within which granulocytic MDSC express CD15, whereas monocytic MDSC express CD66b. More studies are needed to characterize and delineate MDSC subsets in humans. Here we report a preliminary study of myeloid subsets found within a monocyte fraction elutriated from apheresis samples of pediatric cancer patients vs healthy controls. In 4 of 20 pediatric cancer patients studied, we observed accumulation of CD14-CD123-CD11cint or hi cells, which were not present in healthy donors. Further analysis of these abnormal myeloid populations revealed HLA DR+CD127+CD15+CD66b+CD124+ as well as CD68+CD11b+PDL1+, but CD33lo or -. Histologic examination showed these were immature neutrophils and eosinophils. Functional studies demonstrated diminished T cell proliferation in the presence of suboptimal concentrations of OKT3, compared to cultures with CD14+ monocytes and CD14-CD123+CD11c+ myeloid cells, which enhanced T cell proliferation. Studies are underway to further characterize function of this unique subset and to explore expression of suppressive mediators such as iNOS, arginase and IDO.
Plasmacytoid dendritic cells are potent mediators of mucosal B cell responses to rotavirus (67.1)
Authors: Deal Emily , Lahl Katharina , Narvaez Carlos , Butcher Eugene , Greenberg Harry 
Published: January 2023

Abstract
Humoral immunity to rotavirus, an intestinal pathogen, confers protection against re-infection. We utilize both the human in vitro and murine in vivo models of rotavirus infection to delineate the role of primary plasmacytoid dendritic cells (pDCs) in initiating B cell responses. Here, we demonstrate that primary human pDCs are necessary and sufficient for B cell activation by rotavirus. This requires very few pDCs, indicating the potency of the stimulus. Intact type I interferon (IFN) recognition by B cells is essential for activation. We extend these findings in vivo, demonstrating that murine pDCs and IFNα/β also mediate B cell activation following oral rotavirus infection. Furthermore, rotavirus-specific antibody responses are defective in mice lacking functional pDCs at the time of infection. These data demonstrate, for the first time, that B cell activation and virus-specific antibody secretion in response to mucosal viral infection occur as a direct result of pDC-derived type I IFN. Importantly, we observe increased viral shedding in pDC-deficient mice, indicating that pDC-instructed B cells impact viral clearance. We conclude that pDCs, through rotavirus recognition and subsequent type I IFN production, critically influence the course of rotavirus infection. Thus, mucosal pDCs can display powerful adjuvant properties to initiate humoral immunity. Our findings may extend to other mucosal pathogens, such as HIV or influenza.
Bi-specific MHC heterodimers for the characterization of cross-reactive T cells (67.13)
Authors: Shen Zu , Brehm Michael , Daniels Keith , Sigalov Alexander , Selin Liisa , Welsh Raymond , Stern Lawrence 
Published: January 2023

Abstract
T cell cross-reactivity describes the phenomenon whereby a single T cell can recognize two or more different peptide antigens presented in complex withMHCproteins. Cross-reactive T cells have previously been characterized at the population level by cytokine secretion and MHC tetramer staining assays, but single-cell analysis is difficult or impossible using these methods. In this study, we describe development of a novel peptide-MHC heterodimer specific for cross-reactive T cells. MHC-peptide monomers were independently conjugated to hydrazide or aldehyde-containing cross-linkers using thiol-maleimide coupling at cysteine residues introduced into recombinant MHC heavy chain proteins. Hydrazone formation provided bi-specific MHC heterodimers carrying two different peptides. Using this approach we prepared heterodimers of the murine class I MHC protein H-2Kb carrying peptides from lymphocytic choriomeningitis virus and vaccinia virus, and used these to identify crossreactive CD8[|#1#|] T cells recognizing both lymphocytic choriomeningitis virus and vaccinia virus antigens. A similar strategy could be used to develop reagents to analyze cross-reactive T cell responses in humans.
Preferential induction of protective T cell responses to Theiler’s virus in resistant (C57BL/6 x SJL)F1 mice (67.14)
Authors: Jin Young-Hee , Kang Hyun Seok , Mohindru Mani , Kim Byung S. 
Published: January 2023

Abstract
Infection of the CNS with Theiler's murine encephalomyelitis virus (TMEV) induces an immune-mediated demyelinating disease in susceptible mouse strains such as SJL/J (H-2(s)), but not in strains such as C57BL/6 (H-2(b)). In addition, it has been shown that (SJL/J x C57BL/6)F1 mice, which carry both resistant and susceptible MHC haplotypes (H-2(b/s)), are resistant to both viral persistence and TMEV-induced demyelinating disease. In this study, we further analyzed the immune responses underlying resistance of F1 mice. Our study shows that the resistance of F1 mice is associated with a higher level of the initial virus-specific H-2(b)-restricted CD8(+) T cell responses vs. the H-2(s)-restricted CD8(+) T cell responses. In contrast, pathogenic Th17 responses to viral epitopes are lower in F1 mice compared to that in susceptible SJL mice. Dominant effects of resistant genes expressed in antigen-presenting cells of F1 mice on regulating viral replication and inducing protective T cell responses appear to play a crucial role in disease resistance. Although the F1 mice are resistant to disease, the level of viral RNA in the CNS was intermediate between those of SJL/J and C57BL/6 mice, indicating the presence of a threshold of viral expression for pathogenesis.
TGF-beta 1 as outcome marker in patients with influenza A H1N1 (67.18)
Authors: Martinez-Mejia Corazon , Rendon-Ramirez Erik , Rendon Adrian , Salinas.Carmona Mario , Rosas-Taraco Adrian 
Published: January 2023

Abstract
Cytokines and interferons are important molecules involved in influenza control. However, the relation between those cytokines and the outcome of those patients is not clear. The aim of this work was to analyze interferons, proinflammatory and anti-inflammatory cytokines in patients with influenza A H1N1 and other respiratory diseases. Methodology: Healthy controls (n=8), patients with influenza A H1N1 confirmed by PCR (n=14), and patients with other respiratory diseases (n=22) were enrolled. Blood samples were collected from each individual and sera were obtained for cytokines analysis. A panel of 14 cytokines was analyzed: IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-15, IL-17, TNFa, IFNa and IFNg by Luminex; and IL-29 and TGF-b1 by ELISA. Results: IL-6, IL-8, and IL-10 were higher (P&lt;0.05) in sera of patients with influenza A H1N1 and other respiratory diseases compared with control group at admission day. These cytokines were also higher in A H1N1 patients who deceased as compared to those that recovered (P&lt;0.05). TGFb1 was lower in all patient groups compared with control (P&lt;0.05). Interestingly, TGF-b1 increased in A H1N1 patients that recovered. This phenomenon was not observed in other respiratory diseases. No differences were found in the other analyzed cytokines. In conclusion, the anti-inflammatory response, under control of IL-10, is coadjuvated by TGF-b1 which seems important for A H1N1 patient survival.
Caveolin-1 suppresses HIV-1 replication through NF-kappa B. (67.21)
Authors: Simmons Glenn , Hildreth James 
Published: January 2023

Abstract
Caveolin-1 is an integral membrane protein expressed in macrophages. Caveolins are primarily responsible for the formation of intracellular vesicles known as caveolae, which are involved in protein trafficking and cholesterol homeostasis. It has been demonstrated that overexpression of caveolin-1 in cells suppresses HIV-1 protein expression. We have shown that HIV-1 transcription was down-modulated by caveolin-1 expression and the reduction of endogenous caveolin-1 showed an enhancement of HIV-1 replication in cells. Caveolin has been previously demonstrated to blunt inflammatory response via Nf-kappa B. Therefore we tested the role of Nf-kappa B in caveolin-1-mediate HIV-1 suppression. Using HIV-1 reporters with mutations in the Nf-kappa B binding site, we observed a loss of caveolin-mediated suppression on the HIV-1 promoter. From the work presented in this study we concluded that caveolin-1 requires Nf-kappa B in order to suppress HIV-1.
Role of the mannose receptor (CD206) in ricin toxin pathogenesis (99.16)
Authors: Gage Emily , Hernandez Maria , O'Hara Joanne , McCarthy Elizabeth , Mantis Nicholas 
Published: January 2023

Abstract
The entry of ricin toxin into macrophages and other cell types is proposed to occur through two distinct pathways. The first involves the toxin’s B subunit (RTB), an R-type lectin that binds to cell-surface glycolipids and glycoproteins bearing terminal β1,4-linked galactose residues. The second involves recognition of ricin’s mannose side chains by the mannose receptor (MR; CD206), a C-type lectin that functions in both scavenging of serum glycoproteins and uptake of microbial pathogens. While much is known about the role of RTB in ricin uptake, much less is understood about the contribution of the MR in ricin pathogenesis. In this study, we demonstrate using the human monocyte cell line, THP-1 that the MR does indeed mediate toxin uptake and contribute to ricin-induced cell killing in vitro. To determine the role of the MR in ricin toxicity in vivo, MR knock-out mice (MR-/-) or age-matched wild type controls were challenged with 2.5 or 5 lethal dose 50s (LD50s) of ricin, administered by intraperitoneal injection. We found that mice lacking the MR were more susceptible to toxin-induced death than control animals, suggesting that the MR promotes toxin clearance rather than productive internalization, as has been proposed. These findings have implications for the development of biodefense therapeutics aimed at rapidly ridding the toxin from circulation.
Identifcation of new antigen targets for leprosy serodiagnosis (99.24)
Authors: Estrada-Garcia Iris , Talavera-Paulin Moises , Serafin-Lopez Jeanet , Estrada-Parra Sergio 
Published: January 2023

Abstract
Mycobacterium leprae , a non-cultivable bacteria, is the causative agent of leprosy. Despite huge effort from WHO leprosy remains a public health problems in some parts of the world. One of the principal goals of leprosy research is to develop serological tests that will allow identification and early treatment of leprosy patients. In this work, M. habana a cultivable non-pathogenic mycobacterium and candidate vaccine for leprosy, was used to obtain soluble antigenic extracts (MHSE). By Western blot (WB) analysis MHSE proteins were reacted with sera form lepromatous leprosy patients (LL), active tuberculosis patients (TB) and healthy donors (H) from an endemic leprosy area. LL sera diluted 1:2,000 showed reactivity with a 28-30 KDa doublet antigen in MHSE. No reactivity with these bands was observed at 1:2,000 or lower sera dilutions of TB or H donors. After performing two dimension PAGE and WB analysis with the same sera, the doublet band was shown to have several spots. Further characterization was done using Tandem Mass Spectrometry (LC/ESI-MS/MS) and two proteins were identified: enoyl- coenzyme A hydratase (lipid metabolism) and antigen 85B (Ag85B, mycolyltransferase). These proteins represent promising candidates for the design of a reliable tool for the serodiagnosis of the infectious form of leprosy.
Induction of a polyreactive IgM response by bacterial infection (99.26)
Authors: Jones Derek , Winslow Gary 
Published: January 2023

Abstract
Infection of mice with the bacterium Ehrlichia muris induces a protective T cell-independent (TI) IgM response. A unique property of the TI IgM produced during early infection is that it is polyreactive; that is, it binds a number of unrelated foreign and self antigens, including influenza virus, Borrelia burgdorferi, ss- and dsDNA, insulin, and thyroglobulin. We hypothesized that polyreactivity results from cross-reactivity of antigen-specific IgM, or that antibodies of unrelated specificity were generated via polyclonal B cell activation. To address these hypotheses, we generated B cell hybridomas from infected spleen cells and determined whether they produced pathogen-specific IgM. Eighty percent of the IgM-producing hybridomas were ehrlichia-specific; 10% of the IgM bound an immunodominant ehrlichial antigen, OMP-19, and the remainder bound yet unidentified ehrlichial antigen(s). Polyreactivity was exclusively associated with OMP-19-specific IgM, however, indicating that the properties of the antigen (e.g., spatial distribution on the bacterium) influence the selection of polyreactive IgM. These data indicate that polyreactive IgM is generated by antigen-specific B cells. Our data support a model whereby polyreactivity among antigen-specific IgM allows for the heteroligation (Mouquet et al., 2010) of OMP-19 and additional ehrlichial antigens, and serves to increase the relative affinity of IgM.
Suppression of lethal toxicity in Mycoplasma arthritidis-infected mice by blocking PAI-1 is mediated by TLR4-dependent iTreg function (99.28)
Authors: Mu Hong , Cole Barry , Jiang Hua , Nourian Maziar 
Published: January 2023

Abstract
Mycoplasma arthritidis causes arthritis and toxic shock syndrome in natural infections of rodents. Here we show that the level of type 1 plasminogen activator inhibitor (PAI-1), the primary inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), are markedly increased in toxic shock-susceptible mouse strains injected with live M. arthritidis. We also showed that M. arthritidis-infected mice exhibited severe toxic shock syndrome with elevated levels of pro-inflammatory cytokines TNFα, IL-1β, but lower levels of TGFβ and IL-10 production. Repeated injections of animals with anti-PAI-1 blocking antibody effectively prevented mice from lethal toxicity and suppressed production of inflammatory cytokines. Importantly, anti-PAI-1 treatment resulted in increased levels of TGFβ and IL-10 expression and production in vivo. Parallel results demonstrated that the expression of Foxp3, GITR and CTLA-4, the signature markers of inducible regulatory T cells (iTreg) in splenic CD4+ cells, were significantly increased in anti-PAI-1-injected mice with M. arthritidis infection. In addition, we also demonstrated that presence of functional TLR4 is indispensable for the induction and function of iTreg in our model system. Thus these results reveal a novel role of PAI-1 and its association with TLR4 in lethal toxicity caused by M. arthritidis, and suggest it could be a potential therapeutic target for the treatment of inflammatory diseases.
Th17 cells play a central role in experimental Candida albican keratitis in mice (99.32)
Authors: Wang Yiqiang , Zhang Hongbo , Li Hongxia , Zou Yanli , Song Wengang , Jia Changkai , Li Siyuan , Xu Liang 
Published: January 2023

Abstract
Our previous studies showed that experimental Candida albican keratitis (CaK) induced an adaptive immune response. Here we explored the role of T lymphocytes in the progress of CaK. Balb/c mice and nude mice on Balb/c background were used for CaK model. CaK was induced by intrastromal injection of Candida albicans spores into the corneas. Keratitis was measured by scoring the lesions. One day before CaK induction, unsorted splenocytes or purified T cells from either Balb/c, C57BL/6 or OVA-TCR Tg DO11.10 mice were adoptively transferred into nude mice, or various T cell subtypes were depleted in Balb/c mice using specific antibodies. We found that, upon challenge with same amount of fungal spores, Balb/c mice developed typical CaK, but nude mice did not show any sign of CaK. Reconstitution of nude mice with either splenocytes or purified T cells built sensitivity of nude mice to CaK induction in a way dependent of numbers but not of MHC- nor TCR-restriction of transferred cells. Depleting Th17 cells with anti-IL17 or anti-IL23 antibodies completely abrogated the capability of Balb/c mice to develop CaK. But depleting Treg cells with anti-CD25 or γδT cells with anti-γδ antibody did not show any effect. Th17 depleted mice did not set up immunological memory either after primary CaK. We conclude that a minimum of Th17 cells are essential in the initiation of fungal keratitis, and T cells play a dual role in the pathogenesis and prognosis of fungal keratitis.
Parallel expansion of natural Foxp3+ regulatory T cells and effector CD4+ T cells recognizing the same Mycobacterium tuberculosis epitope (99.4)
Authors: Shafiani Shahin , Kaur Sukhraj , Siddiqui Imran , Dinh Crystal , Urdahl Kevin 
Published: January 2023

Abstract
We have previously shown that regulatory T (T reg) cells restrict immunity during early Mycobacterium tuberculosis (Mtb) infection. Our experiments using T cell receptor (TCR) transgenic T reg cells suggest that T reg cells responding during Mtb infection are pathogen-specific. Nevertheless, the epitopes recognized by T reg cells have not been defined in tuberculosis or other infections. Using MHC class II tetramers containing an immunodominant Mtb epitope (specific for ESAT-64-17:I-Ab), we found that a fraction of Foxp3+ T reg cells in the pulmonary lymph node (pLN) of B6 mice during early Mtb infection were specific for ESAT-64-17, the same epitope recognized by effector CD4+ T cells. These T reg cells peaked in number at day 21 when their abundance ranged between 7-20% of all tetramer-binding cells, and disappeared by day 30-40. Interestingly, they were never observed in the lungs. ESAT-64-17-specific T reg cells expressed the transcription factor Helios, whose expression has been linked to thymically-derived natural T reg cells, suggesting that they expand from the population of pre-existing T reg cells and are not derived from conventional ESAT-64-17-specific CD4+ T cells. Moreover, ESAT-64-17-specific T reg cells use a different profile of T cell receptors than effector CD4+ T cells. We hypothesize that the expansion of pathogen-specific T reg cells may not occur in all infections, but may be driven by Mtb to assist in establishing persistent infection.
Group B streptococci Ib monoclonal antibodies protect against invasive aspergillosis. (99.7)
Authors: Wharton Rebekah , Dizon Brian , Kearney John 
Published: January 2023

Abstract
Aspergillus fumigatus (A.f.) the cause of invasive Aspergillosis (IA) has become a leading cause of death in immunosuppressed populations, due to the lack of effective therapies or vaccines. Studies using anti-A.f. monoclonal antibodies indicate that they can protect against IA. However, the lack of detailed information on the antigenic targets of protective anti-A.f. antibodies has hampered the development of an effective anti-A.f. vaccine. It is known that sialylated epitopes found on a variety of pathogens including fungi and Group B Streptococci (GBS) are involved in attachment to host cells, uptake by phagocytes, and complement activation. A.f. sialylated epitopes may therefore provide a potential target for new therapies. Our preliminary data show that a purified, calcium-dependent GBSIb-specific antibody, SMB19 (IgM,κ) also binds to A.f. and provides a degree of protection in a murine model of IA. Likewise, immunization of wild type and SMB19 VH bearing immunoglobulin transgenic mice with a GBSIb vaccine also provides protection. These results support our hypothesis that induction of GBSIb specific antibodies, perhaps supplemented with antifungal drugs, will lead to new vaccines or passive antibody prophylaxis to prevent and treat IA.
The impact of methamphetamine use on host immune response to herpes simplex virus type 2 (105.15)
Authors: Valencia Frances , Milligan Gregg , Cunningham Kathryn , Bourne Nigel 
Published: January 2023

Abstract
Methamphetamine (METH) use is associated with increased risk for sexually transmitted infections (STIs) that is not believed to be due to increased behavioral risk factors alone. However, the impact of METH at the time of exposure to an STI has not been explored. We hypothesized that METH would impact normal host immune responses to an STI pathogen, herpes simplex virus type 2 (HSV-2), resulting in alterations in disease. Female C57BL6 mice were treated with METH (10 mg/kg) or saline daily for 5 days, and inoculated intravaginally with HSV-2 on treatment day 3. METH treated mice experienced significantly earlier onset of disease and enhanced disease progression compared to controls. Unexpectedly, METH treated mice had increased IFNγ levels in the genital tract early after challenge, but this did not correlate with decreased vaginal virus titers. Subsequently, later after virus challenge there were significantly less IFNγ secreting CD4+ T cells in the genital tract of METH treated mice, but an increased number of these cells in the iliac lymph nodes. Our studies confirm our hypothesis that METH alters immune responses to intravaginal HSV-2 challenge with a corresponding impact on disease progression. The alterations in IFNγ production in the genital tract are of particular interest because of the important role of this cytokine in HSV-2 control. These findings have important public health implications and may be more broadly applicable to other important STI’s such as HIV.
The Relationship of Cytomegalovirus (CMV) Infection with circulatory IFN-α levels and IL-7 receptor α expression on CD8+ T cells in Human Aging (105.16)
Authors: Lee Naeun , Lee Won-Woo , Shin Min Sun , Kang Youna , Jeon Sangchun , Kang Insoo 
Published: January 2023

Abstract
The IL-7 receptor alpha (IL-7Rα) is the high affinity receptor for IL-7 which is essential for T cell homeostasis. We recently reported an age-associated expansion of human effector memory (EM) CD8+ T cells expressing IL-7Rα low (IL-7Rαlow), which could be detrimental to hosts by occupying “immunological space”. We investigated the potential mechanisms for this phenomenon, focusing on cytomegalovirus (CMV) infection and IFN-α. In the elderly (age≥65), CMV infection was associated with a decreased frequency of naïve CD8+ T cells as well as with an increased frequency of total EM and IL-7Rαlow EM CD8+ T cells. However, in the young (age≤40), this viral infection was associated only with an increased frequency of IL-7Rαlow EM CD8+ T cells. There was no association found between CMV immune status and plasma levels of IFN-α. In CMV-infected young and elderly people, IFN-α levels had no correlation with the frequency of IL-7Rαlow EM CD8+ T cells although this cytokine levels correlated with the frequency of IL-7Rαlow CD45RA+ EM CD8+ T cells in CMV-uninfected elderly people. Our findings suggest that the effect of CMV infection on CD8+ T cell subsets may begin with IL-7Rαlow EM CD8+ T cells and spread to other subsets with aging. Also, IFN-α could be associated with the expansion of IL-7Rαlow CD45RA+ EM CD8+ T cells in the CMV-uninfected elderly.