bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergy of IL-1 and stem cell factor in radioprotection of mice is associated with IL-1 up-regulation of mRNA and protein expression for c-kit on bone marrow cells.
Authors: Neta R , Oppenheim J J , Wang J M , Snapper C M , Moorman M A , Dubois C M 
Published: December 2022

Abstract
Administration of IL-1 and stem cell factor (SCF) to mice 18 h before lethal 60Co whole-body irradiation resulted in synergistic radioprotection, as evidenced by increased numbers of mice surviving 1,200 to 1,300 cGy doses of radiation and the recovery of increased numbers of c-kit+ bone marrow cells at 1 and 4 days after the lethal dose of 950 cGy. Anti-SCF Ab inhibited IL-1-induced radioprotection, indicating that endogenous production of SCF is necessary for radioprotection by IL-1. Conversely, radioprotection induced by SCF was reduced by anti-IL-1R Ab, indicating that endogenous IL-1 contributes to SCF radioprotection. SCF, unlike IL-1 does not induce hemopoietic CSFs and IL-6 or gene expression of a scavenging mitochondrial enzyme manganese superoxide dismutase in the bone marrow, suggesting that SCF and IL-1 radioprotect by distinct pathways. The mRNA expression for c-kit (by Northern blot analysis) and 125I-SCF binding on bone marrow cells was elevated within 2 and 4 h of IL-1 administration respectively. Four days after LD 100/30 radiation the recovery of c-kit+ bone marrow cells was increased sixfold in IL-1-treated mice, almost 20-fold in SCF-treated mice, and 40-fold in mice treated with the combination of the two cytokines. Thus, endogenous production of both IL-1 and SCF is required for resistance to lethal irradiation and the synergistic radioprotective effect of the two cytokines may, in part, depend on IL-1 and SCF-induced increases in numbers of c-kit+ hemopoietic stem and progenitors cells that survive lethal irradiation.
T cell receptor V delta 2-C alpha transcripts are present in the thymus but virtually absent in the periphery.
Authors: Giachino C , Rocci M P , Bottaro M , Matullo G , De Libero G , Migone N 
Published: December 2022

Abstract
To investigate whether the V delta 2-(D)-J alpha gene configuration, characteristically associated with the major subset of acute lymphoblastic leukemias in humans, might have a physiologic role in T cell ontogeny, we have looked for V delta 2-C alpha transcripts in the thymus and peripheral blood of normal donors. Here we show by PCR analysis that these transcripts are virtually absent in the PBMC, whereas they are present in fetal and postnatal thymus. Interestingly, over 80% of 43 V delta 2-C alpha cDNAs randomly isolated from one postnatal thymus appeared to maintain an open reading frame. This suggests that in the thymus the V delta 2-C alpha products might be exposed to selective pressure. Furthermore, in two of three thymuses tested for J alpha usage, it was found overrepresented in a J alpha element (J alpha 58) located 2 kb downstream to a pseudo-J (J alpha 61), known to be a hot spot of recombination in alpha beta committed cells. A possible alternative pathway to alpha beta T cell differentiation via a V delta 2-J alpha intermediate is discussed.
Chemical and serologic characterization of human lambda VIII light chains.
Authors: Solomon A , Weiss D T , Murphy C , Fu S M , Robbins D L 
Published: December 2022

Abstract
The primary structural features and serologic properties of a newly recognized human lambda light (L) chain V region subgroup (V lambda VIII) were elucidated through study of two monoclonal L chains, Bence Jones proteins HAG and BIV. The V region amino acid sequences of these components were highly homologous to each other and to that deduced from the prototypic V lambda VIII cDNA, Humla8f10, which encodes the L chains of the IgM lambda rheumatoid factor HAF10. Proteins HAG and BIV could be classified as members of the V lambda VIII subgroup and distinguished from L chains of the V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI subgroups on the basis of amino acid sequence. In addition to distinctive residues found within the V lambda gene-encoded portion of the molecules, L chains HAG, BIV, and HAF10 contained remarkably different second complementarity-determining regions (CDR2) that consisted of 11 residues, rather than the seven typically found among members of the other five V lambda subgroups. This elongated structure would presumably impart to the ligand-binding site of lambda VIII molecules a markedly different canonical structure compared with those of lambda I, lambda II, lambda III, lambda IV, and lambda VI L chains. By using Bence Jones protein HAG as an immunogen, we obtained polyclonal and monoclonal anti-V lambda VIII subgroup-specific Abs that were used to identify and quantify lambda VIII-related molecules in normal and pathologic states. Among the Ig lambda components present in the serum of normal individuals, approximately 3% had lambda VIII L chains, a frequency comparable to that found among monoclonal Ig lambda proteins or surface(s) Ig lambda+ cells obtained from patients with malignant plasma cell- or B cell-related disorders, respectively. In contrast, lambda VIII L chains were detected on approximately 19% of monoclonal IgM lambda rheumatoid factors produced by B cell lines established from PBLs or synovial cells from patients with rheumatoid arthritis. The results of our studies provide new information on the structural and immunochemical features of lambda VIII L chains and the possible functional importance of the human V lambda VIII subgroup.
Effect of exogenous fatty acids with greater than 22 carbon atoms (very long chain fatty acids) on superoxide production by human neutrophils.
Authors: Hardy S J , Ferrante A , Poulos A , Robinson B S , Johnson D W , Murray A W 
Published: December 2022

Abstract
The effects of exogenous long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA) on superoxide production by human neutrophils were compared. Superoxide production was greater and more rapid in response to arachidonic (20:4 (n-6)), eicosapentanoic (20:5 (n-3)), and docosahexanoic (22:6 (n-3)) acids than for triacontatetranoic (30:4 (n-6)), dotriacontatetranoic (32:4 (n-6)), and tetratriacontahexanoic (34:6 (n-3)) acids, although all of these fatty acids gave responses larger than FMLP. A similar decline in activity with increasing carbon chain length was observed for the monoenoic VLCFA (22:1 (n-9) to 34:1 (n-9)). 32:4 (n-6) did not affect responses to a maximally stimulatory concentration of 20:4 (n-6). However, the simultaneous addition of 20:4 (n-6) and 30:4 (n-6) gave additive responses if suboptimal dosages of 20:4 (n-6) were used. This suggests that the LCFA and VLCFA may use the same signal transduction systems. In addition, 30:4 (n-6) was only 10% as effective as was 20:4 (n-6) at gaining access to the organic solvent extractable cellular fraction. This figure correlated with the relative biologic potency of 20:4 (n-6) and 30:4 (n-6), suggesting that the extent of association with the cell may regulate the biologic activity of the fatty acids. The saturates, arachidic (20:0) and cerotic (26:0) acids, were either inactive or poor activators in all assay systems examined. The failure of 20:0 to induce superoxide production and the lower responses to 30:4 (n-6) and 34:6 (n-3) were not because of extracellular Ca2+, because the biologic potency of these fatty acids was not greatly enhanced by removing Ca2+ from the extracellular medium. In contrast, 20:4 (n-6)- and 22:6 (n-3)-induced superoxide production was markedly increased under Ca(2+)-free conditions.
FK506 inhibits graft-versus-host disease and bone marrow graft rejection in murine recipients of MHC disparate donor grafts by interfering with mature peripheral T cell expansion post-transplantation.
Authors: Blazar B R , Taylor P A , Fitzsimmons W E , Vallera D A 
Published: December 2022

Abstract
FK506 was evaluated as the sole graft-vs-host disease (GVHD) preventive agent in murine recipients of fully allogeneic donor grafts. FK506 (36 mg/kg given as a suspension on days 0 through 13, then three times per wk through day 29 post-bone marrow transplantation (BMT)) reproducibly led to 50 to 90% of FK506-treated recipients surviving a 60- to 103-day observation period. High doses of cyclosporin A did not protect mice from lethal GVHD. A kinetic study performed in mice that received FK506 demonstrated that mature donor CD3+, CD4+, and CD8+ T cells in the spleen were each reduced by &gt; or = 64%, as compared with vehicle-treated control mice, although this effect was short lived. Thymic reconstitution studies revealed a remarkable decrease in mature CD4+ cells and cells expressing the activation Ag, CD69. In contrast, less mature CD4+8+ thymocytes were not reduced significantly and total thymocyte numbers were only marginally decreased. The fact that peripheral reconstitution of CD4+8- or CD8+4- T cells was impaired significantly at this time indicated that FK506 had a major effect on thymic maturation and/or thymic emigration. In two models specifically designed to study alloengraftment, recipients of pan-T cell-depleted (TCD) donor marrow and FK506 were noted to have accelerated hemopoietic recovery and augmented long-term multilineage peripheral blood alloengraftment, in marked contrast to controls (86 to 97% mean donor cells vs 0% in controls for all lineages). These data demonstrate that FK506 prevents GVHD and graft rejection in vivo by inhibiting mature T cell expansion post-BMT.
TCR V beta family repertoire and T cell activation markers in Kawasaki disease.
Authors: Pietra B A , De Inocencio J , Giannini E H , Hirsch R 
Published: December 2022

Abstract
Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the United States. The etiology is unknown. Data regarding the presence of T cell activation and its potential role in the pathogenesis of the disease have been conflicting. Expansion of T cells bearing V beta 2 and V beta 8 has recently been reported in the acute phase of KD, which suggests that a superantigen may mediate the disease process. To further assess the potential role of T cells in KD, T cell phenotypes were evaluated by using flow cytometry in a large series of patients, acutely and during convalescence. Included in this analysis were assessments of changes in the percentage of T cells bearing TCR V beta 2, V beta 5.1, V beta 6.7, V beta 8, V beta 12.1, and V beta 19 over time; the percentage of each V beta family bearing the activation markers HLA-DR and IL-2R; and the percentage of each V beta family bearing the memory marker, CD45RO. No expansion of any V beta family was present acutely, nor were increases in HLA-DR and IL-2R observed. However, a significant increase was observed during convalescence in the percentage of cells bearing CD45RO in the CD8+, but not the CD4+, population. CD45RO expression was also increased on V beta 2, V beta 8, and V beta 19 CD8+ T cells in a subset of patients. These data suggest that one or more conventional Ags drive the T cell immune response in KD, and argue against a role for superantigens in the disease process.
Endogenous granulocyte-macrophage colony-stimulating factor is involved in IL-1- and IL-7-induced murine thymocyte proliferation.
Authors: Herbelin A , Machavoine F , Vicari A , Schneider E , Papiernik M , Ziltener H , Penit C , Dy M 
Published: December 2022

Abstract
We have reported previously that IL-1 induces murine thymocyte proliferation in the absence of artificial comitogens, provided that the cells are cultured at high densities. In the present study, we show that, in these conditions, TdR uptake in response to IL-1 is diminished significantly by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) Abs. Indeed, a substantial production of this growth factor occurs when thymocytes are cultured in the presence of IL-1. Maximal GM-CSF levels are attained within 3 days of culture, and mRNA expression is detected after a 48-h stimulation. Both GM-CSF production and IL-1-induced thymocyte proliferation are decreased considerably by the depletion of I-A+ Mac-1+ accessory cells. Yet, addition of exogenous GM-CSF to accessory cell-depleted thymocytes does not restore the proliferative response to IL-1 alone, suggesting the implication of another accessory cell-derived mediator. Our data design IL-7 as the endogenous factor required in our culture system because: 1) GM-CSF can reverse the decrease in the proliferation after accessory cell depletion when IL-7 is provided together with IL-1, and 2) the proliferative response to IL-1 plus IL-7 is diminished as much by neutralization of GM-CSF by its specific Abs as by accessory cell removal (approximately 30%). Finally, the cells responding to IL-1 + IL-7 were identified as mature CD4-CD8-TCR+ thymocytes by the use of bromodeoxyuridine (BrdUrd), suggesting that the GM-CSF produced by thymic accessory cells in response to IL-1 participates in IL-7-dependent, intrathymic expansion of the CD4-CD8-TCR+ compartment.
Corneal endothelial cells inhibit T cell proliferation by blocking IL-2 production.
Authors: Kawashima H , Prasad S A , Gregerson D S 
Published: December 2022

Abstract
We have reported that Ia+ LEW rat corneal endothelial (CE) cells could not induce Ag-specific proliferation of MHC compatible T cell lines. Instead, the presence of CE cell monolayers inhibited T cell proliferation assays. We now report on the effect of CE cells on IL-2 production, IL-2R expression, and IL-2 responsiveness of T cells. Ag-specific growth inhibition of the 1C3.4 T cell hybridoma was unaffected by the presence of CE cells but IL-2 production was suppressed by CE cells. Similar CE cell-mediated inhibition of IL-2 secretion was found with fresh splenic lymphocytes stimulated by Con A. Controls showed that neither CE cells nor their supernatant affected the CTLL cell response to rIL-2, allowing reliable measurement of IL-2 production. Further evidence that the block is at the level of IL-2 production was shown by the observation that IL-2R expression was up-regulated after TCR occupancy whether or not CE cells were present. Also, T cells expressing IL-2R were responsive to exogenous rIL-2 whether or not CE cells were present. CE cells themselves do not induce IL-2R expression or IL-2 responsiveness. Under normal culture conditions, the R1170 rat T cell line continually expresses a significant level of IL-2R and dies before IL-2R is down-regulated to background levels. However, in the presence of CE cells, these R1170 cells down-regulate IL-2R and lose IL-2 responsiveness while remaining viable.
Development of intestinal intraepithelial T lymphocytes is independent of Peyer's patches and lymph nodes in aly mutant mice.
Authors: Nanno M , Matsumoto S , Koike R , Miyasaka M , Kawaguchi M , Masuda T , Miyawaki S , Cai Z , Shimamura T , Fujiura Y 
Published: December 2022

Abstract
We have previously reported a new spontaneous recessive mutation that induces a generalized lack of lymph nodes (LNs) and Peyer's patches (PPs) accompanied by immunodeficiency in mice (gene symbol, aly). In this study, we have analyzed gut-associated lymphatic tissues of the mutant aly/aly mice and have compared the intestinal intraepithelial T lymphocytes (IEL) in aly/aly and normal aly/+ littermate mice. Immunohistochemical studies revealed that colonization of IEL and lamina propria T cells takes place in the absence of PPs and IgA-producing B cells in the lamina propria. Absolute numbers of Thy-1- IEL-alpha beta and -gamma delta are not altered in aly/aly mutant mice, whereas absolute numbers of Thy-1+ IEL-alpha beta and -gamma delta in aly/aly mice are about half of those in aly/+ mice. In IEL-alpha beta from aly/aly mice, the major CD8 alpha alpha+ and CD8 alpha beta+ subsets are maintained, whereas CD4+ and CD4+, CD8+ subsets are reduced. Although the population size of major CD8 alpha alpha+ and CD4-, CD8- IEL-gamma delta subsets is slightly reduced, the use of TCR-gamma- and -delta-chain variable gene segments by IEL-gamma delta remains almost the same in aly/aly mice. The constitutive cytolytic activity of IEL-alpha beta and -gamma delta is attenuated sharply in the aly/aly condition. This activity is, however, augmented significantly after in vitro stimulation with anti-CD3 mAb. These results indicate that most of the IEL subpopulations develop independently of passage through PPs and mesenteric LNs and that the aly mutation interrupts cytotoxic IEL development during relatively late differentiation steps that convert cytotoxic precursors to the constitutively cytolytic state.
Immunization of BALB/c mice with recombinant simian virus 40 large tumor antigen induces antibody-dependent cell-mediated cytotoxicity against simian virus 40-transformed cells. An antibody-based mechanism for tumor immunity.
Authors: Bright R K , Shearer M H , Kennedy R C 
Published: December 2022

Abstract
In this report, we describe an immune mechanism that seems to play a role in tumor immunity in BALB/c mice challenged with SV40-transformed cells. This immune mechanism was induced by immunization of mice with rSV40 large tumor Ag (T-Ag). After rSV40 T-Ag immunization, BALB/c mice were protected from a lethal tumor challenge with syngeneic SV40-transformed cells (mKSA). Specifically, we examined CTL activity, NK activity, complement-dependent cytotoxicity, and Ab-dependent cell-mediated cytotoxicity (ADCC) in rSV40 T-Ag-immunized mice that were protected from a subsequent lethal tumor challenge. Immune splenocytes from surviving animals that were subsequently primed in vitro with rSV40 T-Ag demonstrated little to no SV40 T-Ag-specific CTL activity. In addition, natural immunity, as assessed by NK lytic activity, was comparable to that of unimmunized animals. Similarly, minimal significant complement-dependent cytotoxicity of radiolabeled mKSA cells was demonstrated by SV40 T-Ag-specific serum Abs. However, SV40 T-Ag-specific Abs using peritoneal exudate cells as effectors, exhibited significant levels of ADCC against radiolabeled mKSA target cells. Together, these studies indicate that rSV40 T-Ag immunization elicited ADCC that may represent a potential humoral immune mechanism involved in the protection of BALB/c mice from a lethal challenge with syngeneic SV40-transformed cells.
Inhibition of lipopolysaccharide and IL-1 but not of TNF-induced activation of human endothelial cells by suramin.
Authors: Strassmann G , Graber N , Goyert S M , Fong M , McCullers S , Rong G W , Beall L D 
Published: December 2022

Abstract
The binding and trans-endothelium migration of inflammatory cells is believed to play a critical role in a variety of inflammatory conditions. This study investigates the ability of the experimental drug suramin to block the activation of HUVEC by endotoxin and by the proinflammatory cytokines IL-1 and TNF. We demonstrate that the inducible expression of several adhesion molecules by LPS and IL-1 beta but not by TNF-alpha is prevented by suramin. In a dose-dependent manner, suramin inhibits the binding of neutrophils and T lymphocytes to LPS and IL-1 beta but not to TNF-alpha-activated HUVEC. The inhibitory effect of the drug on IL-1 beta-induced but not on LPS-induced cell stimulation can be completely reversed by the addition of excess cytokine but not by excess LPS. Because LPS activation of HUVEC is known to depend on serum/plasma-derived soluble CD14, we set out to determine whether suramin inhibition involves interference with the action of the CD14-LPS complex on HUVEC. Indeed, the drug prevents the binding of radioactive LPS in the presence of serum and inhibits LPS-induced cell activation in serum-free medium supplemented with recombinant soluble CD14. The results suggest that suramin interferes with the CD14-dependent activation of HUVEC and that it also may be a useful agent in blocking infectious endotheliopathies in vivo.
Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1.
Authors: Tumpey T M , Elner V M , Chen S H , Oakes J E , Lausch R N 
Published: December 2022

Abstract
Herpes simplex virus type 1 (HSV-1) infection of the murine cornea induces an intense inflammatory response that can lead to permanent blindness. We tested whether IL-10, a cytokine that has anti-inflammatory properties, could suppress the development of stromal disease. Murine rIL-10 was inoculated intracorneally 4 before and again on days +2 and +5 relative to the time of topical HSV-1 corneal infection. Additionally, the mice received IL-10 i.p. at the time of virus administration and again 3 days post-infection. Four weeks post-infection, the incidence of blinding disease was 95% in the saline-treated controls but only 36% in the IL-10-treated animals. Histologic studies showed extensive cellular infiltrates in control corneas but not in those of the IL-10-treated eyes. Examination of the proinflammatory cytokine levels in the cornea 10 days after infection revealed that the presence of IL-2 was 10-fold lower and IL-6 some 50-fold lower than that found in the controls. IL-1 alpha levels were not reduced. The IL-10 treatment protocol employed did not suppress the systemic cellular or humoral immune responses to viral Ag, nor was the rate of HSV-1 clearance from the eye different from that seen in the controls. In vitro studies revealed that spontaneous production of IL-6 by excised normal corneas was inhibited by &gt; 95% with low dose IL-10. IL-1 alpha synthesis was not inhibited. Collectively, these results indicate that IL-10 treatment can 1) suppress the production of certain cytokines produced by corneal cells, and 2) minimize ocular inflammation without compromising clearance of the infecting virus from the eye.
TNF-alpha production by eosinophils in upper airways inflammation (nasal polyposis).
Authors: Finotto S , Ohno I , Marshall J S , Gauldie J , Denburg J A , Dolovich J , Clark D A , Jordana M 
Published: December 2022

Abstract
TNF-alpha is a cytokine with a wide spectrum of proinflammatory activities. Nasal polyps (NP), which occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of activated eosinophils, epithelial damage, and varying degrees of stromal fibrosis. By using Southern blot analysis after a reverse transcription-PCR, we detected a signal specific for TNF-alpha mRNA in five of seven NP samples, but not in control nasal mucosal samples. With in situ hybridization, we detected cells expressing mRNA specific for TNF-alpha in eight of thirteen NP samples, but not in four control samples. Counterstaining with chromotrope 2R demonstrated that virtually all cells expressing TNF-alpha message were eosinophils. The ratio of eosinophils expressing TNF-alpha to the total number of eosinophils varied greatly among tissues; as an average, we observed 24% TNF-alpha-positive eosinophils. Using a mAb against human TNF-alpha, we demonstrated TNF-alpha localization in 12 NP tissues (48.8 +/- 16.5 positive cells/mm2) but not in three control samples. Morphologically, cells localizing TNF-alpha were both mononucleated and polynucleated with only a small number of eosinophils, as determined by aniline blue counterstaining. Studies of purified blood eosinophils from a patient with hypereosinophilic syndrome and from four healthy donors indicated that TNF-alpha is produced, but rapidly secreted, so that TNF-alpha mRNA-positive cells contain little detectable protein. Furthermore, cells that retain detectable TNF-alpha may not contain sufficient TNF-alpha mRNA to be detected by using the probe developed for our studies. Together, these findings identify a novel mechanism by which eosinophils may contribute to mucosal inflammation and provide an approach to future investigation.