bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation.
Authors: Zúñiga-Pflücker J C , Kruisbeek A M 
Published: December 2022

Abstract
Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells.
Persistence of donor-specific IL-2-secreting cells and cytotoxic T lymphocyte precursors in human kidney transplant recipients evidenced by limiting dilution analysis.
Authors: Lantz O , Alard P , Ben Aribia M H , Chavanel G , Fries D , Senik A , Charpentier B 
Published: December 2022

Abstract
The low reactivity to donor alloantigens reported in PBL from kidney transplant recipients might be related to clonal deletion and/or suppression of donor-specific alloreactive cells. To discriminate between these two hypotheses, we quantified the number of IL-2 secreting cells (IL-2-SC) and of cytotoxic precursors (CTLp) in the T cells from tolerant recipients when stimulated with either donor specific or nonrelated third-party LCL. To eliminate the irrelevant reactivity, we used as responding cells high-density T cells that had been depleted of such reactivity by 4 days preculture with autologous lymphoblastoid cell line in the presence of bromodeoxyuridine. Thus, frequencies of IL-2-SC and CTLp specifically directed at alloantigens could be measured. In 11 recipients, there was no strong decrease in the frequency of donor-reactive T cells when compared to the frequency of those directed at a third-party lymphoblastoid cell line, either for IL-2-SC (tested in 11 patients) or for CTLp (tested in 6 patients). In three cases of seven, a suppression was observed only when T cells were stimulated by donor cells. These data suggest that donor-reactive cells are still present in PBL of kidney-transplant recipients tested from 6 mo to 4 y posttransplantation. Moreover, suppression of donor-specific cells can be demonstrated in peripheral T cells of some recipients, which may account in part for the absence of rejection.
The expanded populations of CD4-CD8- T cell receptor alpha/beta+ T cells associated with the lpr and gld mutations are CD2-.
Authors: Shirai T , Abe M , Yagita H , Okumura K , Morse H C , Davidson W F 
Published: December 2022

Abstract
Mice homozygous for either of two autosomal recessive mutations, lpr and gld, develop massive, generalized lymphoproliferation of CD4-CD8- (double negative, DN) T cells associated with a variety of autoantibodies. To determine the origin of these expanded populations of lpr and gld T cells, we examined the expression of CD2 molecules and mRNA transcripts in association with other cell surface phenotypes of these cells and correlated them with subpopulations of DN T cells in the thymus and peripheral lymphoid tissues. The results indicated that both lpr and gld cells are negative for the transcript and product of the CD2 gene. Both lpr and gld DN T cells were CD2-, CD3+, CD4-, CD8-, CD25-, CD45R+, TCR alpha/beta+, TCR gamma/delta-, HSA(J11d)-/+, Thy-1+/-, and Lp-1-/+. Studies of thymocytes in normal mice using three-color flow cytometry analysis showed that there are at least eight phenotypically distinct populations of DN thymocytes, one of which is similar to lpr and gld cells in terms of CD2-, CD3+, TCR alpha/beta+ and CD25- phenotypes, although they did not express CD45R, HSA, or Lp-1. A very minor population of these CD2-CD3+ TCR alpha/beta+ DN T cells were also detected in peripheral T cells from normal mice. These findings may provide insight into not only the origin of the aberrant lpr and gld T cells but also normal T cell development.
IL-6 functions as an exocrine hormone in inflammation. Hepatocytes undergoing acute phase responses require exogenous IL-6.
Authors: Gauldie J , Northemann W , Fey G H 
Published: December 2022

Abstract
We have previously shown that IL-6 is the major monocyte- and fibroblast-derived regulator of acute phase protein gene expression and synthesis in hepatocytes in inflammation. Recently, we and others have shown that rat and human hepatoma cells express IL-6 mRNA, and the question arose as to whether normal hepatocytes express IL-6 and whether any such expression occurs under normal physiologic conditions or is seen in inflammation. Poly A+ mRNA of liver from normal rats and from rats undergoing an acute phase response was not positive when probed with cDNA for rat IL-6 under conditions in which macrophage mRNA was strongly positive. We then compared poly A+ mRNA from purified hepatocytes freshly isolated from normal rats--from rats that were undergoing an acute inflammatory response and from freshly isolated normal hepatocytes that had been cultured for 24 h in the presence or absence of dexamethasone (microM). Only the mRNA from normal hepatocytes cultured for 24 h in the absence of any glucocorticoid was obviously positive for IL-6. The increased expression of gamma-fibrinogen mRNA indicated the presence of inflammation. These results confirm the identification of IL-6 as an exogenous hormone for regulating normal hepatic acute phase protein synthesis in inflammation and rules out an autocrine mechanism being active in the liver in normal homeostasis.
Evaluation of antisperm complement-dependent immune mediators in human ovarian follicular fluid.
Authors: D'Cruz O J , Haas G G , Lambert H 
Published: December 2022

Abstract
A "sandwich"-type radiolabeled antiglobulin assay using monoclonal anti-C5b-9 neoantigen and polyclonal anti-C5b-9 was used to evaluate the presence of terminal C complexes (SC5b-9 or MC5b-9) in the sera and ovarian follicular fluid (FF) from 45 infertile women. FF SC5b-9 was detectable in all clinical diagnostic categories. The mean SC5b-9 levels in FF and sera were 399 ng/ml (range 75 to 1350 ng/ml) and 798 ng/ml (range 0 to 2700 ng/ml), respectively. Twelve (26.6%) of the 45 FF samples had normal hemolytic C activity, and all FF (n = 44) samples initiated C8/C9-dependent lysis of sensitized sheep E coated with human C1-7. Human plasma IgG antisperm antibodies (ASA) were capable of activating C in 31 (72%) of 43 FF samples as detected by their ability to deposit MC5b-9 on human sperm. Sera from infertile women with ASA in their sera and FF impaired human sperm binding to human zona pellucida and binding and penetration of zona-free hamster oocytes in vitro. The discovery of SC5b-9 and MC5b-9 in ovarian FF implies that the interaction of ASA and C could have a deleterious effect on sperm during in vivo and in vitro sperm-egg interactions in women with antisperm antibodies.
Clonotypes of anti-DNA antibodies expressing specific idiotypes in immune complexes of patients with active lupus nephritis.
Authors: Muryoi T , Sasaki T , Hatakeyama A , Shibata S , Suzuki M , Seino J , Yoshinaga K 
Published: December 2022

Abstract
IEF, using 6 M urea, provides a unique opportunity to analyze the spectrotypes of antibodies in immune complexes (IC) in vivo. Using this technique, we have analyzed the clonotypes of anti-DNA antibodies expressing specific Id in the circulating IC of patients with active lupus nephritis. Serum anti-ssDNA and anti-dsDNA antibodies showed heterogeneous spectrotypes. The antibodies isolated from circulating IC had a restricted clonotype and a neutral charge and were directed mainly to ssDNA and, to a lesser extent, to dsDNA. These samples failed to form complexes with DNA when they were subjected to absorption to a DNA-coupled Sepharose column. Anti-DNA antibodies expressed specific Id, termed O-81 or NE-1, which were detected only in the IC of patients with active lupus nephritis. Anti-DNA clonotypes, including O-81 and NE-1 idiotypes, were also found in the eluates of renal glomeruli of lupus patients. These results indicate that subpopulations of anti-DNA antibodies in circulating IC are limited, and may play an important role in the pathogenesis of lupus nephritis.
C3-cleaving membrane proteinase. A new complement regulatory protein of human melanoma cells.
Authors: Ollert M W , Frade R , Fiandino A , Panneerselvam M , Petrella E C , Barel M , Pangburn M K , Bredehorst R , Vogel C W 
Published: December 2022

Abstract
Human melanoma cells resistant to killing by the R24 mAb and human complement rapidly degrade surface-deposited C3b (M. Panneerselvam, S. Welt, L. J. Old, C.-W. Vogel. 1986. J. Immunol. 136:2534). We report that C-resistant melanoma cells express a membrane proteinase that can cleave C3b, generating a cleavage product with a molecular mass of approximately 30 kDa. The C3-cleaving proteinase was identified on the melanoma cells by its cross-reaction with antiserum to p57, a C3-cleaving proteinase previously isolated from human E membranes (C. Charriaut-Marlangue, M. Barel, R. Frade. 1986. Biochem. Biophys. Res. Commun. 140:1113). Preincubation of the C-resistant melanoma cells with anti-p57 IgG or their F(ab')2 fragments increased their susceptibility to complement killing from 25% to approximately 50% and reduced the rate of C3b cleavage and the amount of the 30-kDa fragment generated on the cells. Anti-p57 IgG stained C-resistant melanoma cells by indirect immunofluorescence and precipitated a protein with an apparent molecular mass of 65 kDa. This membrane protein, termed p65, was not detectable on C-susceptible melanoma cells. Membrane extracts from C-resistant melanoma cells also showed C3-cleaving activity when incubated with purified C3 or C3b, similarly generating a C3 fragment of approximately 35 kDa. This fluid-phase C3 cleaving activity could be partially inhibited by anti-p57 IgG. These data suggest that p65 is a C3-cleaving proteinase, antigenically related to p57, that is expressed on C-resistant melanoma cells and responsible for the C resistance of these cells. We propose that the membrane-bound C3-cleaving proteinase represents another C regulatory protein protecting host cells against killing by C.
Bimodal IgG4-mediated human basophil activation. Role of eosinophils.
Authors: Beauvais F , Hieblot C , Burtin C , Benveniste J 
Published: December 2022

Abstract
The role of IgG4 antibodies in allergic disorders is suspected. Yet, their presence on human basophil membrane has not been demonstrated and the mechanism of the degranulation induced by anti-IgG4 antibodies remains unclear. As previously reported, we observed that monoclonal anti-IgG4 (10 to 100 micrograms/ml) induced histamine release in the presence of D2O from leukocytes of normal and atopic subjects. The release was accompanied by a decrease of the number of toluidine blue-positive basophils (TB+). Histamine release and TB+ decrease were also observed with lower concentrations of anti-IgG4 (1 to 100 pg/ml). Since basophil activation assessed by TB+ decrease was more sensitive than histamine release, we thus used the former method to further study the mechanisms of the anti-IgG4- vs anti-IgE-induced basophil activation. Basophil activation by anti-IgG4 at 1 to 100 pg/ml, but not by anti-IgG4 at 10 to 100 micrograms/ml or anti-IgE, required the presence of polymorphonuclear cells. Furthermore, anti-IgG4-stimulated purified eosinophils, but not neutrophils, released basophil-activating factors identified as cationic proteins from eosinophils. Thus, the human basophil can be activated by anti-IgG4 via two different mechanisms according to the antibody concentration. At high concentrations (10 to 100 micrograms/ml) basophil activation does not require the presence of polymorphonuclear cells whereas at lower concentrations (1 to 100 pg/ml) the presence of eosinophils is necessary. We propose that in the latter concentration range, basophil activation is a two-step process: 1) release by anti-IgG4 of eosinophil cationic proteins that 2) will, in turn, activate human basophils. This study lends support to the role of IgG4 and eosinophils in anaphylactic reactions.
Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin.
Authors: Cirillo R , Triggiani M , Siri L , Ciccarelli A , Pettit G R , Condorelli M , Marone G 
Published: December 2022

Abstract
We have examined the effects of cyclosporin A (CsA) and a series of CsA analogs that bind with decreasing affinity to cyclophilin, to evaluate the involvement of this protein in the release of preformed (histamine) and de novo synthesized (peptide leukotriene C4; LTC4) mediators of inflammatory reactions from human basophils. CsA (8 to 800 nM) concentration-dependently inhibited (5 to 60%) histamine release from peripheral blood basophils challenged with anti-IgE. CsA was more potent (92.6 +/- 1.8 vs 59.1 +/- 4.5%; p less than 0.001) and, at low concentrations, more effective when the channel-operated influx of Ca2+ was bypassed by the ionophore A23187 (IC40 = 24.1 +/- 3.9 vs 105.5 +/- 22.2 nM; p less than 0.05). CsA had no effect on the release of histamine caused by phorbol myristate and bryostatin 1 that activate different isoforms of protein kinase C. Inhibition of histamine release from basophils challenged with anti-IgE was not abolished by washing (three times) the cells before anti-IgE challenge. CsA also inhibited the de novo synthesis of LTC4 from basophils challenged with anti-IgE. The inhibitory effect of CsA was very rapid, and the drug, added from 1 to 10 min during the reaction, inhibited the ongoing release of histamine caused by anti-IgE and by A23187. The experiments with CsA analogs (CsG, CsC, CsD, and CsH) showed that CsH, which has an extremely low affinity for cyclophilin, has no effect on basophil mediator release. In addition, there is a significant correlation between the concentrations of CsA, G, C, and D that inhibited by 30% the histamine release induced by anti-IgE (r = 0.99; p less than 0.001) and by A23187 (r = 0.87; p less than 0.001) and their affinity for cyclophilin.
Release of lactoferrin and elastase in human allergic skin reactions.
Authors: Zweiman B , Kucich U , Shalit M , Von Allmen C , Moskovitz A , Weinbaum G , Atkins P C 
Published: December 2022

Abstract
Our previous skin chamber studies have shown prominent accumulation of viable neutrophils in human allergic skin reaction sites. To determine whether such neutrophils release components that may be pathogenic in allergic reactions, we have compared the patterns of release of five components: 1) lactoferrin, present in specific granules; 2) and 3) elastase and myeloperoxidase, present mainly in azurophilic granules; 4) lactic dehydrogenase, a cytosolic component generally released during cell damage; 5) histamine, present in mast cells and basophils but not in neutrophils. In 13 pollen-sensitive subjects we found that continuous antigen challenge for 5 h lead to a peak of histamine release into overlying skin chambers during the 1st h, followed by a plateau of low level histamine release over the succeeding 4 h. In contrast, there was no significantly increased released of lactoferrin or elastase during the first h, but significantly increased accumulation of these components at Ag challenge sites over the next 4 h. There was no significant difference at Ag vs buffer control sites in the levels of either myeloperoxidase or lactic dehydrogenase. The increased levels of lactoferrin and elastase at antigen challenge sites in the 2nd to 5th h were not simply a reflection of the greater numbers of neutrophils present in such sites because the levels of these components did not correlate significantly with the number of neutrophils in chamber fluids obtained from individual sites. However, such lactoferrin levels did correlate significantly with the amount of histamine released earlier during the 1st h of Ag challenge at individual sites. These findings suggest a selective in vivo release of neutrophil components in IgE-mediated human allergic skin reactions, possibly related in degree to earlier mast cell activation. Inasmuch as lactoferrin likely plays a role in reactive oxidants effects and elastase is a potent nonspecific protease, release of these agents could play a pathogenic role in late phase allergic reactions.
Human humoral immunity to hsp70 during Trypanosoma cruzi infection.
Authors: Engman D M , Dragon E A , Donelson J E 
Published: December 2022

Abstract
Immunologic screening of cDNA expression libraries has been widely used for the identification of DNA sequences encoding the immunologically relevant proteins of many pathogenic microorganisms. For reasons that are not entirely clear, sequences encoding 70-kDa heat shock and related proteins (hsp70), which are among the most highly conserved proteins known, have routinely been identified by this approach. Consequently, hsp70 proteins have been proposed to be involved in the autoimmune processes thought responsible for the pathogenesis of the diseases caused by some of these organisms, e.g., chronic Trypanosoma cruzi infection (Chagas' disease). Therefore, we investigated whether hsp70 might be a specific target of the human humoral immune response to T. cruzi infection, and, if so, whether humoral autoimmunity to hsp70 might play a role in pathogenesis. We found that hsp70 is indeed a major polypeptide Ag in Chagas' disease, but that the antibodies to T. cruzi hsp70 do not react with human hsp70--even though the proteins display 73% amino acid sequence identify. These results indicate that self-tolerance to hsp70 is maintained during chronic T. cruzi infection and strongly argue against a role for humoral autoimmunity to hsp70 in the pathogenesis of Chagas' disease.
The gene sequence and some properties of protein H. A novel IgG-binding protein.
Authors: Gomi H , Hozumi T , Hattori S , Tagawa C , Kishimoto F , Björck L 
Published: December 2022

Abstract
The gene for protein H, a novel bacterial cell wall protein with specific affinity for human IgG Fc, was cloned from a group A Streptococcus and expressed in Escherichia coli. Recombinant E. coli cells produced two forms of a human IgG Fc-binding protein, one with an apparent Mr of 42 kDa in a periplasmic fraction and the other with an apparent Mr of 45 kDa in a mixed fraction of cytoplasms and membranes. Both 42-kDa and 45-kDa protein preparations similarly bound to human IgG1 to IgG4, human IgG Fc, and rabbit IgG, but not to IgG of mouse, rat, bovine, sheep, goat, and human IgA, IgD, IgE, and IgM. The complete nucleotide sequence of the cloned 1.8-kb DNA fragment was determined. An open reading frame encoded a hypothetical protein of 376 amino acid residues (Mr = 42,498). The N-terminal amino acid sequence, consisting of 41 residues, which was removed post-translationally had typical characteristics of Gram-positive bacterial signal peptides. Thus, the mature form of protein H was suggested to consist of 335 residues (Mr = 38,162). There were 3 repeated sequences consisting of 42 residues that were highly homologous to those of protein Arp, an IgA-binding streptococcal cell wall protein, and streptococcal M6 and M24 proteins. The C-terminal amino acid sequence consisting of 93 residues, directly following the repeated sequences, was also highly homologous to that of M6 and M24 proteins. No sequence homology was found between protein H and protein A or protein G, two other IgG-binding bacterial cell wall proteins.
Identification of a single non-H-2 gene regulating graft-versus-host disease response.
Authors: Fast L D 
Published: December 2022

Abstract
Non-MHC loci have been shown to play an important role in the development and regulation of graft-vs-host disease (GVHD). In the murine model of GVHD under study, injection of C57BL/6 spleen cells into unirradiated (C57BL/6 x DBA/2)F1 hybrid recipient mice results in an acute form of GVHD characterized by CTL, suppressor cells, and runting. In contrast, injection of DBA/2 spleen cells into the same recipients results in a chronic form of GVHD that is characterized by a lack of CTL and hyperproduction of Ig and autoantibodies. After preliminary studies with the use of congenic mice showed that non-MHC loci were controlling GVHD responses in this model, genetic analysis of GVHD response of BXD recombinant inbred strains and (B10.D2 x DBA/2) X DBA/2 BC mice identified a single locus, Gvh, on chromosome 7 that controls whether acute or chronic GVHD results from injection of parental lymphocytes into unirradiated (C57BL/6 x DBA/2)F1 recipient mice.
Fine specificity and idiotype diversity of a murine anti-HLA-DQw3 monoclonal antibody elicited with a syngeneic antiidiotypic monoclonal antibody.
Authors: Shinji T , Ono R , Ferrone S 
Published: December 2022

Abstract
A total of 469 hybridomas was generated from a BALB/c mouse immunized with the syngeneic antiidiotypic mAb KO3-34 that recognizes an idiotope within the Ag-combining site of the immunizing syngeneic anti HLA-DQw3 mAb KS13. One of the hybridomas, named S2B154, was shown with a number of serologic and immunochemical assays to mimic the specificity of anti HLA-DQw3 mAb KS13. This result was unexpected, because the antiidiotypic mAb had been classified as gamma because of the lack of detection of anti-HLA-DQw3 antibodies in sera from BALB/c mice immunized with the antiidiotypic mAb KO3-34. The antiidiotypic mAb S2B154, an IgG1, displays a lower affinity constant to HLA-DQw3 Ag-bearing lymphoid cells than mAb KS13, an IgG2b, but a higher one to antiidiotypic mAb KO3-34. Testing with a panel of antiidiotypic mAb elicited with the mAb KS13 showed that both antiidiotypic mAb S2B154 and mAb KS13 express in their Ag-combining site the idiotopes recognized by the antiidiotypic mAb KO3-256, KO3-335, and R1-38. However, the antiidiotypic mAb S2B154 does not react with the mAb R18-9 that recognizes an idiotope outside the Ag-combining site of mAb KS13. The results we have presented question the validity of the classification of antiidiotypic antibodies based on their ability to inhibit the binding of the corresponding antibodies to Ag and on the specificity of antisera elicited with antiidiotypic antibodies. Furthermore, the hybridomas we have developed in this Id cascade provide us the opportunity to analyze the structural basis of idiotypic Ag mimicry and to evaluate the regulatory properties of antiidiotypic antibodies in the immune response to HLA class II Ag.