bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualization, Fate, and Pathogenicity of Antigen-Specific CD8+ T Cells in the Graft-Versus-Host Reaction
Authors: Yu Xue-Zhong , Bidwell Sasha , Martin Paul J. , Anasetti Claudio 
Published: December 2022

Abstract
To follow the fate of alloreactive T cell effectors in graft-vs-host disease, Ld-specific CD8+ T cells from C57BL/6 2C TCR-transgenic donors were transplanted into sublethally irradiated (750 cGy) Ld+ or Ld− recipients. In Ld− C57BL/6 or (BALB/c-dm2 × C57BL/6)F1 recipients, naive 2C T cells engrafted and survived long term, but did not acquire effector function. In Ld+ (BALB/c × C57BL/6)F1 recipients, 2C T cells engrafted, expanded, became cytolytic, destroyed host B cells and double-positive thymocytes, and later disappeared. Despite marked damage to lymphoid and hemopoietic cells by 2C T cells, no significant pathology was detected in other organs, and recipients survived. Ld+ (BALB/c × C57BL/6)F1 recipients died when LPS/endotoxin was administered on day 7 after cell transfer, while Ld− (BALB/c-dm2 × C57BL/6)F1 recipients survived. Our findings show that under certain conditions, a CD8+ T cell population recognizing an extremely limited repertoire of Ags can initiate graft-vs-host disease.
Peripheral CD4+ T Cell Maturation Recognized by Increased Expression of Thy-1/CD90 Bearing the 6C10 Carbohydrate Epitope
Authors: Gui Ming , Wiest David L. , Li Jin , Kappes Dietmar , Hardy Richard R. , Hayakawa Kyoko 
Published: December 2022

AbstractThe SM6C10 IgM autoantibody recognizes a surface determinant, 6C10, that is highly expressed on all immature thymocytes. In contrast, its expression on peripheral T cells appears developmentally regulated, i.e., absent from most naive T cells in spleen of neonatal mice, but expressed on 40–80% of naive CD4+ T cells in adult. In this paper, we demonstrate that SM6C10 recognizes a carbohydrate epitope on the Thy-1 glycoprotein using immunoprecipitation analysis, by binding to affinity-purified Thy-1 in an ELISA, and by sensitivity to N-glycosidase-F treatment. Retroviral Thy-1 gene transduction experiments into Thy-1− variant T cell lines and a pro-B cell line provide evidence that 6C10 glycosylated Thy-1 expression is not restricted to T cells but depends on the recipient cell. Therefore, differences in 6C10 levels among Thy-1+ T cells in mice likely reflect developmental regulation of posttranslational modification of the Thy-1 glycoprotein. The ability of naive CD4+ T cells to respond to anti-Thy-1 stimulation increases from neonate to adult, and 6C10− naive cells from adult mice respond poorly compared with 6C10+ cells, similar to the cells in neonatal mice. These results suggest that there is functional maturation by peripheral CD4+ T cells that coincides with 6C10 glycosylated Thy-1 up-regulation, and natural autoantibody recognizes this 6C10 carbohydrate epitope.
Distinct Mechanisms Target Stress and Extracellular Signal-Activated Kinase 1 and Jun N-Terminal Kinase During Infection of Macrophages with Salmonella
Authors: Procyk Katarzyna J. , Rippo Maria Rita , Testi Roberto , Hoffmann Fred , Parker Peter J. , Baccarini Manuela 
Published: December 2022

Abstract
The interaction between bacteria and macrophages is central to the outcome of Salmonella infections. Salmonella can escape killing by these phagocytes and survive and multiply within them, giving rise to chronic infections. Cytokines produced by infected macrophages are involved in the early gastrointestinal pathology of the infection as well as in the induction and maintenance of the immune response against the invaders. Jun N-terminal kinases (JNK) are activated by inflammatory stimuli and play a role in cytokine production. We have investigated the signaling routes leading to JNK activation in Salmonella-infected macrophages and have discovered that they differ radically from the mechanisms operating in epithelial cells. In particular, activation of the JNK kinase stress and extracellular-activated kinase 1 (SEK1) and of JNK in macrophages occurs independently of actin rearrangements and of the GTPases Cdc42 and Rac, essential mediators in other cells. Activation of JNK is effected by a novel pathway comprising tyrosine kinase(s), phosphoinositide 3-kinase and, likely, atypical protein kinase C ζ. SEK1 is stimulated by a distinct mechanism involving phosphatidylcholine-phospholipase C and acidic sphingomyelinase. Dominant-negative SEK1 can block JNK activation by LPS, but not by Salmonella. These data demonstrate that SEK1 and JNK are activated independently in Salmonella-infected macrophages and offer experimental support for the concept that incoming signals can direct the selective coupling of downstream pathways to elicit highly specific responses. Inhibitors of stress kinase pathways are receiving increasing attention as potential anti-inflammatory drugs. The precise reconstruction of stimulus-specific pathways will be instrumental in predicting/evaluating the effects of the inhibitors on a given pathological condition.
Immune-Associated Nucleotide-1 (IAN-1) Is a Thymic Selection Marker and Defines a Novel Gene Family Conserved in Plants
Authors: Poirier Ghislaine M. C. , Anderson Graham , Huvar Arne , Wagaman Pamela C. , Shuttleworth John , Jenkinson Eric , Jackson Michael R. , Peterson Per A. , Erlander Mark G. 
Published: December 2022

AbstractPositive selection of thymocytes is a complex and crucial event in T cell development that is characterized by cell death rescue, commitment toward the helper or cytotoxic lineage, and functional maturation of thymocytes bearing an appropriate TCR. To search for novel genes involved in this process, we compared gene expression patterns in positively selected thymocytes and their immediate progenitors in mice using the differential display technique. This approach lead to the identification of a novel gene, mIAN-1 (murine immune-associated nucleotide-1), that is switched on upon positive selection and predominantly expressed in the lymphoid system. We show that mIAN-1 encodes a 42-kDa protein sharing sequence homology with the pathogen-induced plant protein aig1 and that it defines a novel family of at least three putative GTP-binding proteins. Analysis of protein expression at various stages of thymocyte development links mIAN-1 to CD3-mediated selection events, suggesting that it represents a key player of thymocyte development and that it participates to peripheral specific immune responses. The evolutionary conservation of the IAN family provides a unique example of a plant pathogen response gene conserved in animals.
A Cyclophilin B Gene Encodes Antigenic Epitopes Recognized by HLA-A24-Restricted and Tumor-Specific CTLs
Authors: Gomi Shinya , Nakao Masanobu , Niiya Fumihiko , Imamura Yutaka , Kawano Kouichiro , Nishizaka Shinya , Hayashi Akihiko , Sobao Yuji , Oizumi Kotaro , Itoh Kyogo 
Published: December 2022

AbstractWe have studied Ags recognized by HLA class I-restricted CTLs established from tumor site to better understand the molecular basis of tumor immunology. HLA-A24-restricted and tumor-specific CTLs established from T cells infiltrating into lung adenocarcinoma recognized the two antigenic peptides encoded by a cyclophilin B gene, a family of genes for cyclophilins involved in T cell activation. These two cyclophilin B peptides at positions 84–92 and 91–99 induced HLA-A24-restricted CTL activity against tumor cells in PBMCs of leukemia patients, but not in epithelial cancer patients or in healthy donors. In contrast, the modified peptides at position 2 from phenylalanine to tyrosine, which had more than 10 times higher binding affinities to HLA-A24 molecules, could induce HLA-A24-restricted CTL activity against tumor cells in PBMCs from leukemia patients, epithelial cancer patients, or healthy donors. PHA-activated normal T cells were resistant to lysis by the CTL line or by these peptide-induced CTLs. These results indicate that a cyclophilin B gene encodes antigenic epitopes recognized by CTLs at the tumor site, although T cells in peripheral blood (except for those from leukemia patients) are immunologically tolerant to the cyclophilin B. These peptides might be applicable for use in specific immunotherapy of leukemia patients or that of epithelial cancer patients.
Nematode Infection Enhances Survival of Activated T Cells by Modulating Accessory Cell Function
Authors: Liwski Robert S. , Lee Timothy D. G. 
Published: December 2022

AbstractThe type of immune response generated following exposure to Ag depends on a variety of factors, including the nature of the Ag, the type of adjuvant used, the site of antigenic entry, and the immune status of the host. We have previously shown that infection of rodents with Nippostrongylus brasiliensis (Nb) shifts the development of type 1 allo-specific responses toward type 2 immunity, suggesting nematode modulation of T cell activation. In this report we explore the immunomodulatory effects of Nb on T cell activation. We found that spleen cells from Nb-infected mice exhibited dramatically increased proliferation in response to Con A and anti-CD3. This hyperproliferation could be transferred in vitro to naive splenocytes by coculture with mitomycin C-treated cells from Nb-infected animals. The transfer was mediated by non-T accessory cells and supernatants derived from Con A-activated non-T cells, suggesting the involvement of a soluble factor secreted by accessory cells. The accessory cells secreted high levels of IL-6, and anti-IL-6 treatment abrogated the supernatant-induced hyperproliferation, thus confirming that IL-6 was mediating the effect. Further, spleen cells from Nb-infected mice were more resistant to activation-induced cell death (AICD) following mitogenic stimulation. Reduced AICD was also transferable and IL-6 dependent. Thus, the hyperproliferation was in part due to enhanced activated T cell survival. These phenomena mediated by accessory cells may contribute to the powerful polyclonal activation of type 2 immunity caused by nematode infection.
Relative Contribution of LFA-1 and Mac-1 to Neutrophil Adhesion and Migration
Authors: Ding Zhi-Ming , Babensee Julia E. , Simon Scott I. , Lu Huifang , Perrard Jerry L. , Bullard Daniel C. , Dai Xiao Y. , Bromley Shannon K. , Dustin Michael L. , Entman Mark L. , Smith C. Wayne , Ballantyne Christie M. 
Published: December 2022

AbstractTo differentiate the unique and overlapping functions of LFA-1 and Mac-1, LFA-1-deficient mice were developed by targeted homologous recombination in embryonic stem cells, and neutrophil function was compared in vitro and in vivo with Mac-1-deficient, CD18-deficient, and wild-type mice. LFA-1-deficient mice exhibit leukocytosis but do not develop spontaneous infections, in contrast to CD18-deficient mice. After zymosan-activated serum stimulation, LFA-1-deficient neutrophils demonstrated activation, evidenced by up-regulation of surface Mac-1, but did not show increased adhesion to purified ICAM-1 or endothelial cells, similar to CD18-deficient neutrophils. Adhesion of Mac-1-deficient neutrophils significantly increased with stimulation, although adhesion was lower than for wild-type neutrophils. Evaluation of the strength of adhesion through LFA-1, Mac-1, and CD18 indicated a marked reduction in firm attachment, with increasing shear stress in LFA-1-deficient neutrophils, similar to CD18-deficient neutrophils, and only a modest reduction in Mac-1-deficient neutrophils. Leukocyte influx in a subcutaneous air pouch in response to TNF-α was reduced by 67% and 59% in LFA-1- and CD18-deficient mice but increased by 198% in Mac-1-deficient mice. Genetic deficiencies demonstrate that both LFA-1 and Mac-1 contribute to adhesion of neutrophils to endothelial cells and ICAM-1, but adhesion through LFA-1 overshadows the contribution from Mac-1. Neutrophil extravasation in response to TNF-α in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased.
A Novel LPS-Inducible C-Type Lectin Is a Transcriptional Target of NF-IL6 in Macrophages
Authors: Matsumoto Makoto , Tanaka Takashi , Kaisho Tsuneyasu , Sanjo Hideki , Copeland Neal G. , Gilbert Debra J. , Jenkins Nancy A. , Akira Shizuo 
Published: December 2022

AbstractC-type lectins serve multiple functions through recognizing carbohydrate chains. Here we report a novel C-type lectin, macrophage-inducible C-type lectin (Mincle), as a downstream target of NF-IL6 in macrophages. NF-IL6 belongs to the CCAAT/enhancer binding protein (C/EBP) of transcription factors and plays a crucial role in activated macrophages. However, what particular genes are regulated by NF-IL6 has been poorly defined in macrophages. Identification of downstream targets is required to elucidate the function of NF-IL6 in more detail. To identify downstream genes of NF-IL6, we screened a subtraction library constructed from wild-type and NF-IL6-deficient peritoneal macrophages and isolated Mincle that exhibits the highest homology to the members of group II C-type lectins. Mincle mRNA expression was strongly induced in response to several inflammatory stimuli, such as LPS, TNF-α, IL-6, and IFN-γ in wild-type macrophages. In contrast, NF-IL6-deficient macrophages displayed a much lower level of Mincle mRNA induction following treatment with these inflammatory reagents. The mouse Mincle proximal promoter region contains an indispensable NF-IL6 binding element, demonstrating that Mincle is a direct target of NF-IL6. The Mincle gene locus was mapped at 0.6 centiMorgans proximal to CD4 on mouse chromosome 6.
Src-Regulated Extracellular Signal-Related Kinase and Syk-Regulated c-Jun N-Terminal Kinase Pathways Act in Conjunction to Induce IL-1 Synthesis in Response to Microtubule Disruption in HL60 Cells
Authors: Cambien Béatrice , Millet Marie-Ange , Schmid-Antomarchi Heidy , Brossette Nicole , Rossi Bernard , Schmid-Alliana Annie 
Published: December 2022

AbstractA microtubule reorganization is often observed during cellular contacts that are associated to IL-1 production. Here, we show that in HL60 cells, vincristine, a microtubule-disrupting agent that induces a strong production of IL-1, triggers the activation of both extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK-1). While ERK activation is rapid and transient, peaking at 10 min, the JNK1 activation is delayed and more sustained reaching a maximum at 2 h. ERK activation was blocked by CP 118556, indicating it is regulated by a Src-like kinase, while JNK1 was inhibited by piceatannol, revealing an upstream regulation by Syk. Each kind of the nonreceptor tyrosine kinase blockers efficiently inhibits the vincristine-induced IL-1 production and diminishes the level of IL-1 transcripts, indicating that the ERK and JNK pathways act coordinately to elicit the transcription of the IL-1 gene. Furthermore, we found that pertussis toxin, a blocker of Go/Gi proteins, abrogated the vincristine-induced activation of both Src and Syk. Our data support a model where the status of microtubule polymerization influences the activity of Go or Gi proteins that control, in turn, two independent Src/ERK and Syk/JNK1 cascades that are both necessary to sustain IL-1 synthesis.
Role of IL-6 in the Pleurisy and Lung Injury Caused by Carrageenan
Authors: Cuzzocrea Salvatore , Sautebin Lidia , De Sarro Giovambattista , Costantino Giuseppina , Rombolà Laura , Mazzon Emanuela , Ialenti Armando , De Sarro Angela , Ciliberto Gennaro , Di Rosa Massimo , Caputi Achille P. , Thiemermann Christoph 
Published: December 2022

Abstract
In the present study we used IL-6 knockout mice (IL-6KO) to evaluate the role of IL-6 in the inflammatory response caused by injection of carrageenan into the pleural space. Compared with carrageenan-treated IL-6 wild-type (IL-6WT) mice, carrageenan-treated IL-6KO mice exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung myeloperoxidase activity and lipid peroxidation were significantly reduced in IL-6KO mice compared with those in IL-6WT mice treated with carrageenan. Immunohistochemical analysis for nitrotyrosine and poly(A)DP-ribose polymerase revealed a positive staining in lungs from carrageenan-treated IL-6WT mice. No positive staining for nitrotyrosine or PARS was found in the lungs of the carrageenan-treated IL-6KO mice. Staining of lung tissue sections obtained from carrageenan-treated IL-6WT mice with an anti-cyclo-oxygenase-2 Ab showed a diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-6WT mice. The intensity and degree of the staining for cyclo-oxygenase-2 and inducible nitric oxide synthase were markedly reduced in tissue sections obtained from carrageenan-treated IL-6KO mice. Most notably, the degree of lung injury caused by carrageenan was also reduced in IL-6KO mice. Treatment of IL-6WT mice with anti-IL-6 (5 μg/day/mouse at 24 and 1 h before carrageenan treatment) also significantly attenuated all the above indicators of lung inflammation. Taken together, our results clearly demonstrate that IL-6KO mice are more resistant to the acute inflammation of the lung caused by carrageenan injection into the pleural space than the corresponding WT mice.
Induction of Experimental Autoimmune Graves’ Disease in BALB/c Mice
Authors: Kaithamana Shashi , Fan Jilao , Osuga Yutaka , Liang Shan-Guang , Prabhakar Bellur S. 
Published: December 2022

Abstract
We immunized BALB/c mice with M12 cells (H-2d) expressing either mouse (mM12 cells) or human thyrotropin receptor (TSHR) (hM12 cells). Immunized mice developed autoantibodies to native TSHR by day 90 and, by day 180, showed considerable stimulatory Ab activity as measured by their ability to enhance cAMP production (ranging from 6.52 to 20.83 pmol/ml in different treatment groups relative to 1.83 pmol/ml for controls) by TSHR-expressing Chinese hamster ovary cells. These mice developed severe hyperthyroidism with significant elevations in both tetraiodothyronine and triiodothyronine hormones. Tetraiodothyronine levels in different experimental groups ranged from a mean of 8.66–12.4 μg/dl, relative to 4.8 μg/dl in controls. Similarly, mean triiodothyronine values ranged from 156.18 to 195.13 ng/dl, relative to 34.99 ng/dl for controls. Next, we immunized BALB/c mice with a soluble extracellular domain of human TSHR (TBP), or TBP expressed on human embryonic kidney cells (293 cells) (293-TBP cells). These mice showed severe hyperthyroidism in a manner very similar to that described above for mice immunized with the mouse TSHR or human TSHR, and exhibited significant weight loss, with average weight for treatment groups ranging from 20.6 to 21.67 g, while controls weighed 24.2 g. Early after onset of the disease, histopathological examination of thyroids showed enlargement of colloids and thinning of epithelial cells without inflammation. However, later during disease, focal necrosis and lymphocytic infiltration were apparent. Our results showed that conformationally intact ectodomain of TSHR is sufficient for disease induction. Availability of a reproducible model in which 100% of the animals develop disease should facilitate studies aimed at understanding the molecular pathogenesis of Graves’ disease.
The Antigenic Substances of the Tubercle Bacillus
Authors: Dienes L. 
Published: December 2022

Summary
In the extracts of tubercle bacillus obtained with alcohol of different strength and with methyl-alcohol we found six different antigens, three of which are well characterized and well separated from the others. The characterization of three others is not definite. It needs further work to establish the nature of the differences between these antigens and as to whether they have different antigen specificity in the usual sense of this word.
From the watery extract, weak NaOH extract, and broth cultures we separated three protein fractions with different antigenic properties and different isoelectric points. These fractions probably contained different protein substances. Our observations indicate that in the protein substances more than these three antigens are present, and especially in certain watery extracts and in the filtrates of liquid media there is present a protein substance which is non-precipitable with acids, has strong tuberculin effect, and the antigenic properties of which are different from those of the other protein antigens.
The antibody production is strongest with intact bacteria and bacillary fragments. There is a distinct difference between the sera obtained with living and with killed bacillus emulsion. Toward the different antigens varying amounts of antibodies are present in these sera, sometimes the protein antibodies predominate, and lipoid antibodies are not formed—or only slightly formed—in other sera the opposite is the case. Toward two antigens antibodies are not produced. Both the watery and the alcoholic extracts produce antibodies, although in slighter amounts than the formed elements. In the sera produced with the lipoid substances a certain amount of protein antibodies is usually present, and the sera obtained with the 75 per cent alcoholic extract contain in abundance the two types of antibodies which are absent in the sera obtained with bacillus emulsion. With the progress of the purification the antigenic effect in vivo with the majority of the antigen preparations largely decreases or disappears. We observed also that in the purified preparation an antigenic effect in vivo appears which was not present in the original extract, and, especially certain protein fractions, produced precipitins in abundance toward the carbohydrate precipitable substance, while the extracts themselves were ineffective. The majority of antigens in conformity with the conception of Zinsser produced antibodies only when in connection with larger complexes in which certain protein substances have probably a preponderant rôle.
The use of tuberculous guinea pigs for the production of antisera was of great help both for the differentiation of the antigens and for the examination of the antigenic effect in vivo.
A Note on the Paper: “Studies in Isohemag-Glutination”
Authors: Wiener A. S. , Lederer Max , Polayes S. H. 
Published: December 2022

Abstract
In a recent paper by the writers (1), the statement was made that the priority of Landsteiner in the discovery of human isoagglutination has been questioned by Furuhata, who quotes Japanese and Chinese books of the thirteenth century that he claims deal with this subject. Unfortunately the wording was such that we seemed to indorse Furuhata's contention. In the meantime we have learned from information for which we are indebted to Dr. Philip Levine that Furuhata's contention, which by itself appears improbable, is entirely erroneous. The latter, who tried to trace the source of Furuhata's statement, wrote to him and requested him to substantiate it. In his answer to Levine, Furuhata referred to a book edited by H. Breitenstein: “Die Gerichtliche Medizin der Chinese,” by Wang-in-Hoai, Leipsig, 1908, Grieben's Verlag. The following is quoted as it appears in chapter 15 of that volume, which may be procured from the Army Medical Library, Washington, D.C.
The Preparation of Fibrinogen-Free Fowl Serum
Authors: Kyes Preston , Carey Earl S. 
Published: December 2022

Abstract
In a previous publication (1) we have shown that the shock which results from the intravenous injection of an anti-pneumococcus fowl serum into man, may be avoided by so preparing the serum that it is fibrinogen-free. We gave two methods by which such preparation may be accomplished. The preferable method involved the use of calcium chloride and cephalin in favoring complete conversion of fibrinogen into fibrin and we gave details as to the use of those reagents.
We have since further developed this method and it is the purpose of this paper to present the modified procedure.
In obtaining fowl's blood, 30 cc. are allowed to flow from the leg vein of each bird into a tube containing 2 cc. of 3 per cent sodium oxalate and 18 cc. of physiological salt solution.
The cells are removed by centrifugalization and the supernatant plasma pooled.