bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of T cell tolerance by directing a self antigen to macrophage-specific scavenger receptors.
Authors: Abraham R , Choudhury A , Basu S K , Bal V , Rath S 
Published: December 2022

Abstract
Breakdown of immune self tolerance is speculated to cause autoimmune diseases, but most studies on tolerance use foreign molecules as targets. In this study, we show another approach using delivery of a maleylated self protein to macrophage-specific scavenger receptors. Mice generate Abs against the maleylated form of a ubiquitous self Ag, mouse serum albumin (MSA), although native MSA is nonimmunogenic. This generation of anti-maleyl MSA Abs depends on binding of maleyl MSA to scavenger receptors in vivo, since coinjection of a serologically unrelated scavenger receptor ligand inhibits it, suggesting that the Ab response is T cell dependent. Spleen cells as well as nylon adherence-purified splenic T cells from maleyl MSA-immune mice proliferate in response to both maleyl MSA and MSA; this response is blocked by anti-MHC class II mAbs, and the autoimmune cells can recognize at least five 15-mer peptides from the MSA sequence, establishing that T cell tolerance to MSA has been broken in these mice. Maleyl MSA and MSA are recognized equally well, provided the scavenger receptor-specific delivery of maleyl MSA is blocked during stimulation in vitro, indicating that maleyl MSA-specific non-self peptides are unlikely to play a major role in the observed disruption of T cell tolerance. Thus, delivery of some self molecules to scavenger receptors may lead to disruption of immune tolerance. These results are relevant to mechanisms of immune tolerance and the etiopathogenesis of autoimmunity.
Involvement of IL-10 in the autonomous growth of EBV-transformed B cell lines.
Authors: Beatty P R , Krams S M , Martinez O M 
Published: December 2022

Abstract
Immunocompromised individuals have an increased incidence of EBV-associated B cell lymphomas. The growth factors responsible for the unrestrained proliferation of these lymphomas have not yet been determined. In this study, spontaneous lymphoblastoid cell lines (SLCL) were derived without the addition of growth factors or virus from four patients with EBV-associated lymphoproliferative disorder. These cell lines were EBV transformed in vivo, and infection was verified through amplification of the viral gp220 gene. SLCL have an activated B cell phenotype (CD19+, CD21+, CD23+, CD38+, and CD40+) and produce IL-6, IL-10, TNF-alpha, and lymphotoxin-alpha. To determine whether these cytokines contribute to autonomous growth, neutralizing Abs for IL-10, IL-6, and TNF-alpha, a soluble TNFR:Fc fusion protein, and soluble IL-10R were used. These experiments established that, of the cytokines produced by SLCL, only IL-10 is an autocrine factor. IL-10 was produced by the majority of cells within each SLCL, and IL-10 secretion was concomitant with SLCL growth. Our findings demonstrate that IL-10 is utilized in the autonomous growth of EBV-related lymphomas and may be crucial in the development of lymphoproliferative disorder.
Distribution of Ly-6C on lymphocyte subsets: I. Influence of allotype on T lymphocyte expression.
Authors: Schlueter A J , Malek T R , Hostetler C N , Smith P A , deVries P , Waldschmidt T J 
Published: December 2022

Abstract
The expression patterns of the Ly-6C Ag were examined on splenic and thymic lymphocyte subsets of Ly-6.1 and Ly-6.2 strains of mice using the rat mAb 15.1. Ly-6C is expressed on subsets of CD4+ and CD8+ splenocytes, and a portion of NK cells. Within the splenic and lymph node CD4+ T cell compartment, Ly-6C expression is restricted to Ly-6.2 strains of mice, and is present on a subset of naive cells. Ly-6C is expressed on the majority of peripheral CD8+ T cells in both Ly-6.1 and Ly-6.2 strains, and is found primarily on the Ag-experienced subset. In the thymus, Ly-6C is present on subpopulations of CD4- CD8+, CD4- CD8-, and CD4+ CD8- cells. Ly-6C+ CD4- CD8+ thymocytes show a mature phenotype, while Ly-6C+ CD4- CD8- and Ly-6C+ CD4+ CD8- thymocytes appear to be part of the recently described NK1.1+ alphabeta TCR+ population. On account of the marked differences in Ly-6C expression on peripheral CD4+ T cells from Ly-6.1 and Ly-6.2 strains of mice, additional experiments were undertaken to assess Ly-6C expression in parental and Ly-6.1 x Ly-6.2 F1 mice. Neither phenotype dominated in the F1 offspring, with frequencies of Ly-6C+ CD4+ splenocytes falling in the intermediate range. Further experiments compared the staining patterns of the rat anti-pan Ly-6C (Ly-6.1 and Ly-6.2) Ab with a mouse anti-Ly-6.2 allotype specific Ab, with emphasis on both Ly-6.2 and Ly-6.1 x Ly-6.2 F1 mice. The results demonstrate the presence of lymphocytes that express the pan form of Ly-6C but not the form recognized by the alloantibody. This latter finding suggests the presence of more than one form of the Ly-6C Ag.
V(H) repertoire maturation during B cell development in vitro: differential selection of Ig heavy chains by fetal and adult B cell progenitors.
Authors: Marshall A J , Paige C J , Wu G E 
Published: December 2022

Abstract
B cell development is characterized by marked changes in Ig repertoire, which include shifts in the pattern of V(H) segment usage. B cell precursors characteristically utilize a restricted set of V(H) segments, while mature B cell populations use a wide range of V(H) segments. V(H)81x is an example of a V(H) segment that is highly utilized in B cell precursors, but is rarely utilized in mature B cells. To dissect the molecular and cellular requirements for Ig repertoire maturation, we have examined V(H)81x usage in an in vitro model of B cell development. We find that primary fetal or adult B cell progenitors differentiating in vitro mimic progenitors differentiating in vivo with respect to V(H)81x overusage and subsequent decline in V(H)81x usage, showing that neither of these events is dependent on the intact architecture of the primary lymphoid organ or contact with stromal cells. The relative decline in V(H)81x usage in cultures initiated with adult progenitors was associated with a decrease in the ratio of productive/nonproductive V(H)81x-DJ(H) rearrangements; however, an increase in this ratio was observed in identical cultures initiated with fetal progenitors. This result indicates a difference in selection of V(H)81x-encoded heavy chains that is intrinsic to fetal and adult B cell progenitors. Thus, while the relative decline in V(H)81x usage during adult development can be at least partially explained by selection against cells bearing V(H)81x-encoded heavy chains, other mechanisms must be postulated to explain the decline in V(H)81x usage during fetal development.
Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells.
Authors: Multhoff G , Botzler C , Jennen L , Schmidt J , Ellwart J , Issels R 
Published: December 2022

Abstract
Evidence is accumulating that members of the heat shock protein 70 (HSP70) family are found on the cell surface of certain tumor cells where they elicit a strong antitumor immune response. We demonstrated that HSP72, the major heat-inducible form of the HSP70 group, is located on the cell surface of approximately 60% of the human colon carcinoma cells CX2 with two different mAbs by indirect immunofluorescence, by electron microscopy, and by selective cell surface biotinylation. In an effort to analyze the role of HSP72 cell surface expression as a tumor-specific recognition structure within an "autologous" tumor system, the CX2 cells were separated into a stably HSP72 high expressing (CX+: &gt;90%) and a stably HSP72 low expressing (CX-: &lt;20%) subline. The expression "autologous" was written in parentheses to indicate that the colon carcinoma sublines CX+ and CX- derived from the original CX2 tumor cell line differ with respect to the cell surface expression pattern of HSP72, whereas they exhibit an identical cell surface expression pattern of MHC and cellular adhesion molecules (e.g., intercellular cellular adhesion molecule, neural cellular adhesion molecule, vascular cellular adhesion molecule). Within this "autologous" tumor cell system, we demonstrate that the sensitivity to lysis mediated by adherent non-MHC-restricted effector cells correlates (p &lt; 0.05) with the amount of HSP72 that is expressed on the cell surface. Blocking studies using an HSP72-specific mAb revealed that HSP72 might act in an MHC-unrestricted manner as a tumor-specific recognition structure for a distinct NK cell population.
Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils.
Authors: Wirthmueller U , Dewald B , Thelen M , Schäfer M K , Stover C , Whaley K , North J , Eggleton P , Reid K B , Schwaeble W J 
Published: December 2022

Abstract
Properdin is an important regulatory constituent of the complement system. In contrast to most other components of complement, biosynthesis of properdin is restricted to a few cell types only, i.e., monocytes/macrophages and peripheral blood T cells. This report demonstrates the presence of properdin mRNA in peripheral blood granulocytes and shows that properdin is stored in the granules of human neutrophils and secreted upon stimulation with TNF-alpha, C5a, IL-8, or FMLP. Subcellular fractionation using Percoll density gradients and Western blot analyses revealed that the bulk of properdin is contained in the secondary granules. Moreover, flow cytometric analyses indicated that properdin is present on the surface of neutrophils. In contrast to alternative pathway components, components of the classical pathway of complement activation, such as C2 and C4, were not detected. Our findings suggest that neutrophils can actively stabilize and amplify the alternative activation pathway of complement by secretion of properdin as part of the innate defense against microorganisms.
Transgene-induced production of IL-4 alters the development and collagen expression of T helper cell 1-type pulmonary granulomas.
Authors: Lukacs N W , Addison C L , Gauldie J , Graham F , Simpson K , Strieter R M , Warmington K , Chensue S W , Kunkel S L 
Published: December 2022

Abstract
A number of complex mechanisms regulate the size and cellularity of an Ag-dependent granulomatous reaction and their accompanying cytokine production profiles. In the present study, Th1 (purified protein derivative (PPD)) and Th2 (schistosome egg Ag)-type granulomas were established to examine the role of IL-4 in lesion development and procollagen type III expression. PPD-sensitized mice were transfected via the airway with an adenovirus construct containing an IL-4 cDNA cassette, and the lungs were embolized with sized Ag-coated Sepharose beads. Granuloma development in response to the PPD bead challenge in control mice primarily consisted of mononuclear cells. In contrast, the overexpression of IL-4 in the IL-4 adenovirus-transfected animals demonstrated a significant increase in cellularity, size, procollagen type III expression, and accumulation of eosinophils. Analysis of mRNA and protein within the lung demonstrated significant expression of IL-4 in only the IL-4 adenovirus-transfected animals. The granuloma lesion size was significantly increased in the IL-4 adenovirus-transfected animals on days 2 and 5, reaching an approximate 50% increase compared with the control groups. Furthermore, procollagen type III mRNA expression was increased in the IL-4 adenovirus-transfected, PPD bead-embolized lungs. In contrast, when IL-4 was neutralized during Th2-type schistosome egg Ag bead granulomas, a decrease in procollagen type III was observed. These data indicate that the progression of certain granulomas may be regulated by the production of IL-4, thus altering the cellularity, size, and matrix composition of the inflammatory response.
A noncytolytic IL-10/Fc fusion protein prevents diabetes, blocks autoimmunity, and promotes suppressor phenomena in NOD mice.
Authors: Zheng X X , Steele A W , Hancock W W , Stevens A C , Nickerson P W , Roy-Chaudhury P , Tian Y , Strom T B 
Published: December 2022

Abstract
We have been successful in our efforts to develop a long lived noncytolytic murine IL-10/Fc fusion protein. In the nonobese diabetic mouse (NOD) model, administration of IL-10/Fc from 5 to 25 wk of age completely prevented the occurrence of diabetes. Moreover, these mice remained disease-free long after cessation of IL-10/Fc therapy. Immunohistochemistry studies show that IL-10/Fc treatment inhibits expression of TNF-alpha, proinflammatory cytokine, as well as Th1-type cytokines, IL-2 and IFN-gamma, but promotes expression of IL-4 and IL-10, Th2-type cytokines, by islet-infiltrating leukocytes. In an adoptive transfer model of diabetes in NOD mice, we found that: 1) IL-10/Fc treated hosts bear leukocytes that block expression of diabetes and 2) these leukocytes persisted even 8 wk after cessation of IL-10/Fc treatment. The potent antidiabetogenic effects provided by IL-10/Fc in the NOD model, together with its apparent lack of systemic toxicity, are notable.
Inhibition of primary and recall allergen-specific T helper cell type 2-mediated responses by a T helper cell type 1 stimulus.
Authors: Scott D E , Agranovich I , Inman J , Gober M , Golding B 
Published: December 2022

Abstract
Allergic responses are characterized by the production of Ag-specific IgE Abs that are dependent upon Th2-mediated T cell help. We determined whether heat-killed Brucella abortus (BA), an inducer of Th1 responses, could influence the allergic Th2-mediated IgE response to OVA adsorbed to alum (O/A). BA plus O/A, but not O/A alone, induced high levels of mRNA for IFN-gamma and IL-12 promptly after injection. Furthermore, initial treatment with BA plus O/A rendered both BALB/c and C57Bl/6 mice incapable of mounting high IgE responses even after repeated challenges with allergen alone. Long term abrogation of anti-OVA IgE correlated with an increased frequency of IFN-gamma-secreting OVA-specific cells and a decreased frequency of IL-4-secreting OVA-specific cells. Initial treatment with anti-IL-12 prevented BA-induced early IFN-gamma production and secondary IgG2a responses, but did not abrogate IgE suppression. Additionally, secondary OVA-specific IgE responses were down-regulated by BA conjugated to OVA or by BA given with O/A. BA-induced down-regulation of secondary IgE responses was associated with increased frequency of Ag-specific IFN-gamma-secreting cells. These results suggest the possibility that even recall Th2-mediated immune responses can be attenuated if Ag is given with a carrier or adjuvant that induces potent Th1-promoting cytokines.
Bcl-2 expression in target cells leads to functional inhibition of caspase-3 protease family in human NK and lymphokine-activated killer cell granule-mediated apoptosis.
Authors: Renvoizé C , Roger R , Moulian N , Bertoglio J , Bréard J 
Published: December 2022

Abstract
In the granule exocytosis pathway of cell-mediated cytotoxicity, rapid apoptotic nuclear damage in target cells has been unequivocally linked to granzyme B activity. Direct cleavage and activation of caspase-3 and related proteases by granzyme B have been identified as a central event in apoptosis induction by cytotoxic granules. The Bcl-2 oncoprotein has been recently shown to act at the level or upstream of caspase-3 family activation to inhibit apoptosis induced by various stimuli including Fas ligation, an alternative cell-mediated lytic pathway. In this study, we have investigated whether activation of this caspase family by granzyme B, during human NK and lymphokine-activated killer cell granule-mediated apoptosis, could be influenced by Bcl-2 expression. Bcl-2-overexpressing clones were generated from parental K562 and U937 cell lines (K6 and U4 clones, respectively). Bcl-2 expression abrogated early 125I-DNA release and DNA fragmentation, these defects being compensated for by extended incubation times. Cleavage of poly(ADP-ribose) polymerase, a specific caspase-3 family substrate, was detected in parental K562 cells exposed to lymphokine-activated killer effectors but not in K6 targets, indicating that caspase-3 and related proteases function was inhibited by Bcl-2. Functional inhibition of caspase-3 family with benzyloxycarbonyl-Asp-Glu-Val-Asp(OMe) fluoromethylketone led to similar consequences on apoptotic nuclear events as for Bcl-2 expression. Thus, Bcl-2 antagonizes granzyme B-mediated apoptosis by a mechanism that interferes with caspase-3 activity. Finally, Bcl-2 expression or the Asp-Glu-Val-Asp peptide was much less efficient in preventing phosphatidylserine externalization, suggesting that despite impaired nuclear apoptosis, immediate recognition and elimination of Bcl-2-expressing cells by tissue phagocytes should remain partly unaffected.
Ca2+-dependent, Fas- and perforin-independent apoptotic death of allografted tumor cells by a type of activated macrophage.
Authors: Yoshida R , Sanchez-Bueno A , Yamamoto N , Einaga-Naito K 
Published: December 2022

Abstract
Both perforin- and Fas ligand (FasL)-deficient CTLs show impaired lytic activity toward most target cells. In this study, we examined whether these molecules could be involved in the cell-to-cell contact-dependent cytotoxicity mediated by macrophages infiltrating into the rejection site of allografted Meth A fibrosarcoma cells. FasL-expressing lymph node cells from MRL-lpr/lpr mice were inactive toward Meth A tumor cells. In C3H/HeJ-gld/gld (abnormal FasL) mice, allograft-induced macrophages (AIM) were cytotoxic against Meth A cells expressing no Fas Ag. Furthermore, allografted Meth A tumor cells were acutely rejected by both C3H/HeJ-gld/gld and control C3H/HeJ mice, indicating that the cytotoxic activity of AIM against Meth A tumor cells was Fas/FasL independent. On the other hand, the cytotoxic activity of AIM against the allografts was dose dependently inhibited by EGTA; and the suppression was restored by the addition of Ca2+, but not Mg2+, implying the involvement of perforin in the cytotoxicity. In the perforin-deficient mice, however, AIM were cytotoxic against Meth A tumor cells; and allografted Meth A tumor cells were acutely rejected by both perforin-deficient and control B6 mice, indicating a perforin-independent cytotoxicity. Thus, through a yet unknown mechanism, AIM induced the apoptotic death of allografted Meth A tumor cells. These results indicate that AIM-mediated cytotoxicity against allografted Meth A tumor cells is Ca2+ dependent, and that an attack by AIM results in the apoptotic death of allografted Meth A tumor cells through a third mechanism, one other than the Fas/FasL- and perforin-based pathways.
Structure and genomic organization of a second class of immunoglobulin light chain genes in the channel catfish.
Authors: Ghaffari S H , Lobb C J 
Published: December 2022

Abstract
Earlier studies distinguished two classes of catfish light (L) chain (designated F and G). The cDNA structure and genomic organization of G L chain gene clusters has also been characterized previously. In this study, full length cDNA encoding F L chain was derived using PCR strategies based on the determined amino-terminal protein sequence. The encoded V region is readily delineated into framework regions (FR) and complementarity-determining regions (CDR). Multiple sequence alignments indicate that the F V(L) is closely related to kappa gene families. The F C(L) cannot be generally classified but it is structurally distinct from the C(L) regions of G: the amino acid sequence similarity is &lt;35%. cDNA sequences representing processed sterile F transcripts of different loci were identified. Each sequence begins within the J(L) recombination signal sequence and extends downstream through the I(L)-C(L) segments. Genomic blots hybridized with C(L) probes indicate that there are at least 50 different C(L) segments. Based upon V(L) hybridization studies, different families of V(L) segments appear to be associated with closely related F C(L) segments. In characterized genomic clones, F gene segments are arranged in closely linked clusters with single copies of V(L), J(L), and C(L) segments within each cluster. The V(L) segments are located in opposite transcriptional polarity relative to the J(L) and C(L) segments, which indicates that V(L) segments rearrange by inversion. These combined studies establish that two structurally distinct classes of L chains are present in teleost fish and that both of the L chain classes evolved within a common organizational pattern of clustered segmental genes.
Expression of a biologically active recombinant mouse IL-1 receptor antagonist and its use in vivo to modulate aspects of the acute phase response.
Authors: Grehan S , Uhlar C M , Sim R B , Herbert J , Whitehead A S 
Published: December 2022

Abstract
Recombinant mouse IL-1receptor antagonist protein (rmIL-1ra) was expressed in Escherichia coli. In vivo administration of rmIL-1ra, in a casein-induced murine model of acute inflammation, completely abolished the hepatic induction of the mRNAs specifying serum amyloid A1 (A-SAA1) and A-SAA2 for up to 12 h, indicating that hepatic A-SAA mRNA synthesis is totally IL-1 driven. A-SAA protein, however, was present in the serum of rmIL-1ra-treated casein-stimulated mice (although at lower levels than in untreated casein-stimulated mice) at 12 h indicating that extrahepatic A-SAA synthesis is driven in part by factors acting independently of IL-1. Hepatic mRNA levels of the other mouse acute phase reactants (APRs), serum amyloid P component, C-reactive protein, alpha1-acid glycoprotein, and C3 were also induced with casein after 12 h, as were serum protein levels of SAP and C3. These inductions were only partially inhibited by rmIL-1ra, indicating that hepatic expression of the latter APRs (unlike that of A-SAA) is driven partly by IL-1 and partly by factors acting independently of IL-1. Hepatic mRNA levels of the negative APRs apolipoprotein A-I and serum albumin were down-regulated 12 h after casein stimulation. rmIL-1ra partially restored serum albumin mRNA levels but not apo A-I mRNA levels, indicating differential regulation of these negative APRs. The rmIL-1ra will be useful in studies of IL-1-mediated gene regulation in murine models of inflammation.
Endotoxin induces expression of type II phospholipase A2 in macrophages during acute lung injury in guinea pigs: involvement of TNF-alpha in lipopolysaccharide-induced type II phospholipase A2 synthesis.
Authors: Arbibe L , Vial D , Rosinski-Chupin I , Havet N , Huerre M , Vargaftig B B , Touqui L 
Published: December 2022

Abstract
Elevated levels of secretory type II phospholipase A2 (sPLA2-II) have been associated with a poor clinical outcome in the acute respiratory distress syndrome. This study identifies the cell source(s) and the mechanisms of sPLA2-II synthesis in the guinea pig model of acute respiratory distress syndrome induced by intratracheal injection of LPS. Administration of LPS led to an increase in lung membrane-associated calcium-dependent sPLA2 activity, which was abrogated by LY311727, a selective inhibitor of sPLA2-II. No sPLA2 activity was detected in the vascular compartment of the lung. LPS administration induced a parallel accumulation of sPLA2-II mRNA in lung tissues. In situ hybridization showed that sPLA2-II transcripts were synthesized in interstitial and alveolar macrophages (AM). Incubation of AM with LPS enhanced the expression of sPLA2-II mRNA, leading to stimulation of sPLA2-II synthesis and secretion. This increase was prevented by the addition of anti-TNF-alpha and anti-p55 TNF receptor Abs. Furthermore, the addition to AM of cellfree bronchoalveolar fluid collected from LPS-treated guinea pigs increased sPLA2-II expression, which was abrogated by anti-TNF-alpha Ab. These findings demonstrate that 1) macrophages are in vivo the major cell source of sPLA2-II in LPS-induced acute lung injury; 2) in contrast to that in other cell systems, regulation of LPS-induced sPLA2-II synthesis in AM is TNF-alpha dependent; and 3) production of TNF-alpha in the air-lung interface is an important step for sPLA2-II synthesis in macrophages.