bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular analysis of a germ line-encoded idiotypic marker of pathogenic human lupus autoantibodies.
Authors: Young F , Tucker L , Rubinstein D , Guillaume T , André-Schwartz J , Barrett K J , Schwartz R S , Logtenberg T 
Published: December 2022

Abstract
Id-16/6 is an idiotypic marker found in both IgM and IgG antibodies, as well as in the tissue lesions of patients with SLE. The prototypic Id-16/6+ mAb is 18/2, whose VH3-derived H chain is encoded by an unmutated germ-line gene. We found that the H chains of VH3-derived Id-16/6+ antibodies contain the major determinants of Id-16/6. Moreover, B cell clones from which those antibodies were harvested produce RNA that hybridized under conditions of high stringency to oligonucleotide probes corresponding to the CDR of the VH segment of 18/2. Western blots of Id-16/6+ mAbs with anti-Id confirmed the association of the Id with H chains. Id-16/6 can identify a subgroup of VH3-derived antibodies we have termed the 18/2 CDR family. However, Id-16/6 can also be expressed in some antibodies unrelated to the 18/2 CDR family. No characteristic Ag-binding specificity was found among the members of the 18/2 CDR family. The principal phenotypic feature shared by all known members of the family is Id-16/6.
Delineation of the mechanism of inhibition of human T cell activation by PGE2.
Authors: Minakuchi R , Wacholtz M C , Davis L S , Lipsky P E 
Published: December 2022

Abstract
The capacity of PGE2 to inhibit human T cell responses was examined by investigating its effect on mitogen-induced IL-2 production and proliferation of highly purified CD4+ T cells. PGE2 inhibited both PHA and anti-CD3 induced proliferation and IL-2 production by an action directly on the responding T cell. Inhibition of IL-2 production reflected decreased accumulation of mRNA for IL-2. A variety of other cAMP elevating agents exerted similar inhibitory effects. Inhibition of proliferation could be overcome by supplemental IL-2, PMA, or the anti-CD28 mAb 9.3. Although PMA and 9.3 markedly increased the amount of IL-2 produced by mitogen-stimulated T cells, the percentage inhibition of IL-2 secretion caused by PGE2 and other cAMP elevating agents remained comparable in these costimulated cultures. Rescue of T cell DNA synthesis by these agents appeared to reflect the finding that, although PGE2 markedly inhibited IL-2 production, the absolute amount of IL-2 produced was increased sufficiently to sustain mitogen-induced proliferation. As anticipated, PGE2, forskolin, and cholera toxin increased T cell cAMP levels. The quantity of cellular cAMP generated in response to PGE2, cholera toxin, and forskolin could be inhibited by PMA or 2',5'-dideoxyadenosine. Using these reagents, the inhibitory effects of PGE2 were found to reflect intracellular cAMP levels, but only within a very narrow range. The results indicate that by elevating cAMP levels, PGE2 inhibits human T cell IL-2 production at a point that is common to both the CD3 and CD28 signaling pathways.
Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines.
Authors: Miller M D , Wilson S D , Dorf M E , Seuanez H N , O'Brien S J , Krangel M S 
Published: December 2022

Abstract
We previously reported the isolation and characterization of a cDNA clone, I-309, that encodes a small secreted protein produced by activated human T lymphocytes. This protein is structurally related to a large number of recently identified proteins that are secreted upon cellular activation. In this report we describe the isolation and characterization of the gene encoding I-309. The genomic organization is essentially identical to that found in the genes encoding the structurally similar proteins TCA-3, hJE/MCP-1, and mJE, strengthening the hypothesis that these genes are evolutionarily related. The region of the I-309 gene 5' of the mRNA cap site exhibits extensive nucleotide sequence homology with the same region of the murine gene TCA-3, providing additional evidence that I-309 and TCA-3 are likely to be homologs. Finally, panels of rodent-human somatic cell hybrids were used to map the I-309 gene to human chromosome 17. In conjunction with recent mapping data from other laboratories, this result suggests the presence of a cluster of related genes on this chromosome.
In vitro differentiation from a pluripotent human CD4+CD8+ thymic cloned cell into four phenotypically distinct subsets.
Authors: Boumsell L , Schmid M , Dastot H , Gouttefangeas C , Mathieu-Mahul D , Bensussan A 
Published: December 2022

Abstract
Human thymic cell differentiation is almost totally unknown. In the present study we developed an in vitro system using human thymic cloned cells to analyze precursor-progeny relationship. We obtained several CD4+CD8+ double positive thymic clones that could give rise after several weeks in culture only to either CD4 or CD8 single positive clones. By contrast we isolated a unique pluripotent thymic double positive clone, termed B12, which differentiated into four phenotypically distinct T cell clones, namely double-positive CD4+CD8+, double-negative CD4-CD8- or either single-positive phenotype. We derived stable subclones representative of each phenotype and we showed by molecular analysis that they expressed the same TCR. Utilization of either CD3 or anticlonotypic mAb revealed that this TCR expressed by the four subclones was functional.
Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization.
Authors: Kripke M L , Munn C G , Jeevan A , Tang J M , Bucana C 
Published: December 2022

Abstract
These studies address the hypothesis that Ag-bearing epidermal Langerhans cells migrate to the regional lymph node during contact sensitization and function as APC. Skin from C3H mice was grafted onto BALB/c nude mice, and 7 or 14 days later, the recipients were sensitized with FITC through the grafts. APC from lymph nodes draining the site of sensitization were capable of sensitizing C3H recipients to FITC. Because sensitization is MHC restricted, only cells reaching the lymph node from the grafted skin could have induced contact hypersensitivity in C3H mice. Examination of the FITC+ draining lymph node cells by immunofluorescence and immunoelectron microscopy demonstrated that all were Ia+, most were F4/80+, and some contained Birbeck granules. These studies demonstrate that Ia+, FITC+ cells from the skin, at least some of which are Langerhans cells, leave the skin after epicutaneous sensitization with FITC and participate in the initiation of the contact hypersensitivity response within the regional lymph node.
Cloned suppressor T cells derived from mice tolerized with conjugates of antigen and monomethoxypolyethylene glycol. Relationship between monoclonal T suppressor factor and the T cell receptor.
Authors: Takata M , Maiti P K , Kubo R T , Chen Y H , Holford-Strevens V , Rector E S , Sehon A H 
Published: December 2022

Abstract
Cloned Ts cells specific for the Ag, human monoclonal (myeloma) IgG, were derived from spleen cells of mice that had been immunosuppressed by treatment with a tolerogenic conjugate of HIgG and monomethoxypolyethylene glycol. The cloned Ts cells (clone 23.32) suppressed in vitro antibody responses in an Ag-specific and MHC-restricted manner. By FMF with appropriate antibody reagents, these cells were shown to be Thy-1+, CD4-, CD5-, and CD8+ and to express CD3 and the alpha beta-TCR. These results are consistent with the view that Ts cells use Ag recognition structures similar to those reported for Th cells and CTL. A soluble factor (TsF) extracted from the cloned Ts cells also suppressed in vitro antibody responses in an Ag-specific and H-2Kd-restricted manner, i.e., restricted to MHC class I molecules. The suppressive activity of this TsF could be abrogated by addition of mAb H28-710 that reacts with a determinant on the alpha-chain of TCR. Moreover, the TsF bound to and could be recovered from an immunosorbent consisting of the anti-alpha-TCR mAb H28-710 coupled to Sepharose 4B. In contrast, the TsF was not bound by immunosorbents consisting of mAb to the beta-chain of TCR (H57-597) or to V beta 8 (F23.1). It was, therefore, concluded that the TsF of clone 23.32 is serologically related to the alpha-chain of the TCR; however, it is not identical to TCR, because it lacks the determinants expressed on the TCR beta-chain that are recognized by the two anti-beta mAbs used in this study.
Resistance to infection by HIV-1 of peripheral blood mononuclear cells from HIV-1-infected patients is probably mediated by neutralizing antibodies.
Authors: Tremblay M , Numazaki K , Li X G , Gornitsky M , Hiscott J , Wainberg M A 
Published: December 2022

Abstract
We have investigated whether PBMC of HIV-1-seropositive subjects are as susceptible to in vitro infection by HIV-1 as are PBMC from seronegative controls. Accordingly, stimulated PBMC from 19 HIV-1-infected subjects were inoculated with four different variants of HIV-1. None of these cultures produced either detectable quantities of viral reverse transcriptase activity or p24 Ag following inoculation with HIV-1. In contrast, in five of six cases in which these PBMC were depleted of B cells by antibody plus complement prior to viral inoculation, the presence of viral reverse transcriptase and p24 Ag was detected. The presence of normal levels of CD4-Ag at the surface of the CD4+ cells in these populations was established by flow cytometry. Analysis by an immunoblot assay revealed that anti-HIV antibodies were present in the sera obtained from these infected donors; in addition, 7 of 10 culture fluids derived from the nondepleted PBMC were shown to contain virus-neutralizing antibodies. Cultures which were depleted of B cells did not contain detectable levels of antiviral antibodies. Confirmation that the virus produced by the PBMC which had been depleted of B cells was of the strain used to infect the cultures, rather than that which initially caused patient infection, was provided on the basis of differential susceptibility to antibody neutralization. These results suggest that antibodies produced by B cells in cultures of PBMC from seropositive donors may restrict infection by HIV-1 of such cultures under laboratory conditions.
Regulation of IFN-gamma-receptor expression in human monocytes by granulocyte-macrophage colony-stimulating factor.
Authors: Fischer T , Wiegmann K , Böttinger H , Morens K , Burmester G , Pfizenmaier K 
Published: December 2022

Abstract
The regulation of human IFN-gamma receptor (IFN-gamma-R) expression by granulocyte-macrophage CSF (GM-CSF) was investigated. On monocytic cell lines (U937, HL60) and peripheral blood monocytes, IFN-gamma-binding capacity was down-regulated upon incubation with GM-CSF. Scatchard plot analyses revealed that down-regulation was caused by a decrease in IFN-gamma-R number rather than by a change in affinity. GM-CSF treatment did not reduce IFN-gamma-R-specific mRNA levels, but reduced the half-life of membrane-expressed IFN-gamma-R, indicating a post-translational control of IFN-gamma-R by GM-CSF. Because both IFN-gamma and GM-CSF are crucially involved in activation of monocytic function, the data presented suggest that down-regulation of IFN-gamma-R by GM-CSF may represent a potential negative feedback control of monocyte activation. Further studies of IFN-gamma binding characteristics and isolation of IFN-gamma-R by immunoprecipitation revealed that IFN-gamma binding to human peripheral blood monocytes is mediated by a receptor protein structurally and functionally identical to that previously characterized in several established cell lines of other tissue origin.
The role of IFN-gamma in the pathology of experimental endotoxemia.
Authors: Heinzel F P 
Published: December 2022

Abstract
Proinflammatory cytokines provoked by circulating bacterial LPS mediate many of the destructive host responses characteristic of septic shock. To determine if the lymphokine IFN-gamma has a similar pathogenic role during endotoxic shock, mice were pretreated with murine rIFN-gamma (rMuIFN-gamma) at various times relative to challenge with Salmonella enteritidis LPS. Subsequent mortality was increased when rMuIFN-gamma was administered before or up to 4 h after endotoxin challenge. Pretreatment with rMuIFN-gamma resulted in nearly fivefold increases in serum TNF during endotoxemia, but TNF levels were unaffected by IFN administered after endotoxin. The increased levels of serum TNF probably reflected enhanced translation of this factor, as tissue expression of TNF mRNA did not increase correspondingly in IFN-pretreated mice. To examine the role of IFN-gamma produced endogenously during endotoxemia, mice were pretreated with 0.5 mg of anti-IFN-gamma mAb before endotoxin injection. This treatment significantly reduced mortality from endotoxic shock but caused only minor decreases in serum TNF. Anti-IFN-gamma administered 2 h after endotoxin was similarly protective. These results demonstrate a significant role for IFN-gamma in the pathology of septic shock, both indirectly as an activator of monokines known to promote lethality and possibly by other, late-acting mechanisms.
Induction of the heat shock response protects cells from lysis by tumor necrosis factor.
Authors: Kusher D I , Ware C F , Gooding L R 
Published: December 2022

Abstract
A minority of transformed cell lines are directly susceptible to lysis by TNF, whereas many cells can be made sensitive to TNF by treatment with inhibitors of protein synthesis. Other groups have shown that exposure to TNF induces in many cells a transcription/translation dependent response that protects the cell from TNF lysis. Heat shock proteins are involved in protecting cells from the lethal affects of heat and other metabolic poisons. In this report, we test the possibility that heat shock proteins are also involved in protecting cells from lysis by TNF. We find that after induction of the cellular heat shock response by either heat or arsenite treatment, both spontaneously TNF-sensitive cells and those cells made sensitive by inhibition of protein synthesis are nearly completely protected from TNF cytolysis. The heat-treated cells retained most of their capacity to bind TNF, suggesting that heat shock functions at a postreceptor binding phase of the lytic process. Mouse C3HA fibroblasts are also made sensitive to TNF lysis by treatment with cytochalasin E. We have previously found that elicitation of the cell's TNF-protective response by exposure to TNF suppresses killing of C3HA by subsequent treatment with TNF plus cytochalasin E. In contrast, we report here that induction of the heat shock response did not provide significant protection to C3HA from killing by TNF in the presence of cytochalasin E. Thus, although induction of heat shock proteins does protect cells from TNF, they appear to act by a mechanism distinct from that elicited by TNF itself.
Inhibition by dexamethasone of histamine production in allergic inflammation in rats.
Authors: Hirasawa N , Funaba Y , Hirano Y , Kawarasaki K , Omata M , Watanabe M , Mue S , Tsurufuji S , Ohuchi K 
Published: December 2022

Abstract
In an allergic inflammation model of air pouch type in rats, histamine level in the pouch fluid and histidine decarboxylase activity of pouch wall tissues in the postanaphylaxis phase were increased. Although treatment with dexamethasone failed to inhibit histamine release from mast cells in the anaphylaxis phase, histamine production in the postanaphylaxis phase was inhibited dose dependently. Histamine production-increasing activity in the pouch fluid collected 8 h after the Ag challenge, which was estimated by an activity to stimulate histamine production by bone marrow cells, was decreased by the administration of dexamethasone at the time of the Ag challenge. The addition of steroidal antiinflammatory drugs, dexamethasone, prednisolone, or hydrocortisone, into the incubation medium inhibited the pouch fluid-induced histamine production by bone marrow cells. Hydrocortisone mesylate antagonized the inhibitory effect of dexamethasone on histamine production by bone marrow cells. However, hydrocortisone mesylate failed to recover the decrease in histamine production-increasing activity of the pouch fluid collected from dexamethasone-treated rats. In addition, the dialyzed sample of pouch fluid obtained from dexamethasone-treated nonsensitized rats did not reduce the stimulated histamine production by the pouch fluid sample obtained from the sensitized rats. However, increase in histamine production of bone marrow cells stimulated by the pouch fluid was not inhibited by cyclosporin A that inhibited histamine production induced by Con A. This observation indicates that the pouch fluid has no effect to induce production of the histamine production-increasing factor by bone marrow cells. Consequently, it is suggested that dexamethasone inhibits not only the production of histamine production-increasing factor but also the response of histamine-producing cells to this factor.
Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells.
Authors: Patella V , Casolaro V , Björck L , Marone G 
Published: December 2022

Abstract
Peptostreptococcus magnus strain 312 (10(6) to 10(8)/ml), which synthesizes a protein capable of binding to kappa L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 x 10(-2) to 3 micrograms/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca2(+)- and temperature-dependent, optimal release occurring at 37 degrees C in the presence of 1.0 mM extracellular Ca2+. There was an excellent correlation (r = 0.82; p less than 0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p less than 0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C4 as well as histamine. Protein L (10(-1) to 3 micrograms/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C4 and/or PGD2) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 micrograms/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in vitro and in vivo presumably by interacting with kappa L chains of the IgE isotype.
A large degree of functional diversity exists among helper T cells specific for the same antigenic site of influenza hemagglutinin.
Authors: Haberman A M , Moller C , McCreedy D , Gerhard W U 
Published: December 2022

Abstract
The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes.
Immune responses during human Schistosoma mansoni. XVII. Recognition by monoclonal anti-idiotypic antibodies of several idiotopes on a monoclonal anti-soluble schistosomal egg antigen antibody and anti-soluble schistosomal egg antigen antibodies from patients with different clinical forms of infection.
Authors: Montesano M A , Freeman G L , Gazzinelli G , Colley D G 
Published: December 2022

Abstract
A monoclonal human anti-soluble schistosomal egg Ag(SEA) antibody (E5) that stimulates anti-Id T cells and is idiotypically represented in pools of immunoaffinity-purified human anti-SEA antibodies from chronic, generally asymptomatic, intestinal (INT) patients (AM1 and AM5) was used to raise several monoclonal anti-Id: 1C2, 1C6, 4A8, 4F9, and 2A7. Cross-inhibition between these anti-Id identified distinct idiotopes on E5. Anti-SEA preparations from schistosomiasis patients (AM1, AM5, and others) were tested for their inhibition of the E5/monoclonal anti-Id reactions, in competitive ELISA. In either the E5/4A8 or E5/1C6 ELISA system, anti-SEA from INT (AM1 or AM5) or hepatointestinal (HI) (AM7) patients were able to inhibit these reactions. However, anti-SEA antibodies from acute (AM9) or hepatosplenic (HS) (AM3 or AM8) patients did not express Id that were inhibitory in these systems. These results suggest that a relatively high proportion of INT and HI anti-SEA antibodies express a dominant cross-reactive idiotope (CRI) recognized by 1C6/4A8. This CRI is also easily detected in plasmas from individual INT patients. Anti-Id 1C2 reacted strongly with an Id in AM1, AM5, or AM7, but one which also occurred, to a lesser extent, in AM3, AM8, and AM9. Monoclonal anti-Id 4F9 and 2A7 reacted weakly with idiotopes expressed by antibodies from all patients, regardless of the clinical form of their infection. These observations indicate that anti-SEA antibodies from INT and HI, but not acute or HS patients express dominant, CRI that are identified by 1C6, 4A8, or 1C2 and are also expressed on the INT-derived anti-SEA mAb E5.