bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene.
Authors: Weiss A , Shields R , Newton M , Manger B , Imboden J 
Published: December 2022

Abstract
Concanavalin A (Con A), which together with phorbol myristate acetate (PMA) can activate the human T cell line Jurkat to produce interleukin 2 (IL 2), is shown to depend on the expression of the T3/T cell antigen receptor heterodimer (T3/Ti) complex to induce activation. alpha-methyl mannoside was able to reverse all of the observed effects of Con A on intracellular biochemical events. Therefore, ligand-receptor occupancy appears to be required for sustaining biochemical events associated with triggering the T3/Ti complex. Studies of the time-dependent requirements for the two stimuli required for activation revealed that simultaneous stimulation with both Con A and PMA is required for 2 to 4 hr for the cell to commit itself to activation, as measured by the appearance of secreted IL 2. This 2- to 4-hr requirement correlated precisely with the appearance of IL 2 mRNA, and the appearance of IL 2 transcripts depended on protein synthesis during this critical time period.
Syngeneic anti-idiotypic antisera to murine monoclonal antibodies to monomorphic and polymorphic determinants of HLA class I antigens.
Authors: Perosa F , Tsujisaki M , Ferrone S 
Published: December 2022

Abstract
BALB/c mice were immunized with syngeneic anti-HLA class I monoclonal antibodies. The latter included the anti-HLA-A2, A28 monoclonal antibody (MoAb) CR11-351, the MoAb Q6/64 to a determinant restricted to HLA-B antigens and the MoAb CR10-215 and CR11-115 to the same (or spatially close) monomorphic determinant. Anti-idiotypic antibodies could be detected in bleedings obtained 3 days after the first booster, increased in titer in bleedings obtained after the second booster, and persisted at high levels in subsequent bleedings. The four anti-HLA class I MoAb did not differ in their ability to elicit syngeneic anti-idiotypic antibodies. Cross-blocking studies with a panel of anti-HLA class I, anti-HLA class II, and anti-human melanoma-associated antigen (MAA) MoAb showed that the anti-MoAb CR10-215 and anti-MoAb CR11-115 antisera contain only antibodies to private idiotopes, whereas the anti-HLA MoAb CR11-351 and anti-MoAb Q6/64 antisera also contain antibodies to public idiotopes. The latter are expressed by the anti-HLA class I MoAb CR11-351, Q1/28, Q6/64, and 6/31, and by the anti-HLA class II MoAb Q5/6, Q5/13, 127, and 441. Public idiotopes were not detected on the nine anti-MAA MoAb tested. Public idiotopes do not interfere with the binding of anti-HLA MoAb with the corresponding antigenic determinants. On the other hand private idiotopes are located within the antigen-combining site, because anti-idiotypic antisera specifically inhibit the binding of the corresponding immunizing anti-HLA class I MoAb to cultured human lymphoid cells in a dose-dependent manner. Analysis by isoelectric focusing of the anti-HLA class I MoAb antisera showed that the spectrotype of the anti-MoAb CR11-351 antiserum comprises four components that focus in the pH 6.9 to 6.2 range, the spectrotype of anti-MoAb Q6/64 antiserum comprises three components that focus in the pH 6.5 to 6.1 range, the spectrotype of the anti-MoAb CR10-215 antiserum comprises three components that focus in the pH 6.4 to 6.1 range, and the spectrotype of the anti-MoAb CR11-115 antiserum comprises three components that focus in the pH 6.6 to 6.4 range.
Functional analysis of T lymphocyte subsets in antiviral host defense.
Authors: Leist T P , Cobbold S P , Waldmann H , Aguet M , Zinkernagel R M 
Published: December 2022

Abstract
The role of different T cell subsets in antiviral host defense was investigated by treating thymectomized C57BL/6 and CBA/J mice with monoclonal rat anti-Lyt-2 or anti-L3/T4 IgG 2b antibodies 14 and 10 days before infection. This treatment depleted the respective T cell subsets to undetectable levels in peripheral blood when assayed by immunofluorescence. In mice treated with anti-Lyt-2, induction of cytotoxic T cells was reduced to less than 1 to 2% after intravenous infection with Armstrong strain of lymphocytic choriomeningitis virus (LCMV). In addition, no primary swelling of the footpad could be detected following local inoculation of the virus. In animals treated with anti-L3/T4, antiviral cytotoxic T lymphocyte responses were reduced by a factor of 10. These L3/T4+ cell-depleted mice showed delayed footpad swelling after local injection of LCMV Armstrong. After intracerebral infection with LCMV, anti-Lyt-2-treated mice were resistant and those injected with anti-L3/T4 were totally susceptible to LCMV Armstrong-triggered immunopathologic disease. Virus could be detected in the blood of antibody-treated mice 7 days after inoculation; however, no virus could be measured in the blood of surviving anti-Lyt-2-treated animals 15 days after intracerebral infection. Serum titers of interferon-alpha,beta induced by viral infection remained unaffected by depletion of T cell subsets. Anti-L3/T4 antibody-treated C57BL/6 mice failed to generate IgG antibodies against the New Jersey strain of vesicular stomatitis virus, whereas Lyt-2+ cell-depleted mice had normal antivesicular stomatitis virus (New Jersey strain) IgG antibody titers.
Eleven MRL-lpr/lpr anti-DNA autoantibodies are encoded by genes from four VH gene families: a potentially biased usage of VH genes.
Authors: Trepicchio W , Barrett K J 
Published: December 2022

Abstract
The genes encoding 11 independently derived anti-DNA autoantibodies from the lupus-prone mouse strain, MRL-lpr/lpr, were examined with VH, D, and JH gene probes. These autoantibodies do not define new VH gene families, since all of the autoantibodies were encoded by VH genes from four of the nine known gene families. A minimum of nine different VH genes encoded this panel of 11 anti-DNA autoantibodies. These results are consistent with the stochastic use of the VH gene repertoire and the expression of multiple VH genes. However, the data is also consistent with a biased usage of the VH gene repertoire. First, two pairs of autoantibodies, one from the J558 family and one from the 7183 family, appear to express identical or closely related VH genes as determined by the position of two restriction enzyme sites 5' of the expressed VH genes. In addition, three autoantibodies that appear to be sister clones might define a third VH gene that is used repeatedly. Secondly, about 45% of the panel is encoded by the Q52 and 7183 families, which are the 3' most families. These families have been shown to be preferentially rearranged early in B cell ontogeny. This suggests that some anti-DNA autoantibodies might originate from a population of B cells that predominate early in ontogeny. An alternative hypothesis is that the potential bias in VH gene and gene family usage could be due to antigen selection. All four JH genes are expressed, although the JH1 gene appears to be underutilized in both expressed and unexpressed rearrangements. Two members of the panel that bind double-stranded DNA were encoded by two different VH gene families, the S107 family and the J558 family.
T cell receptor genes do not rearrange or express functional transcripts in natural killer cells of scid mice.
Authors: Tutt M M , Schuler W , Kuziel W A , Tucker P W , Bennett M , Bosma M J , Kumar V 
Published: December 2022

Abstract
The lineage of natural killer (NK) cells is poorly understood. To examine the relationship between NK cells and cells of the T lineage we have examined purified NK cells from a mutant mouse strain (scid) with severe combined immunodeficiency. Approximately 40% of the lymphoid cells in the spleens of scid mice expressed the NK-specific marker NK-2.1. All NK activity of the scid spleen cells could be accounted for by the NK-2.1+ population, similar to results obtained by using normal C57BL/6 X DBA/2 (B6D2F1) mice. Sorted NK-2.1+ cells proliferated in response to human recombinant interleukin 2 (r-IL 2) but not to concanavalin A (Con A), and were maintained in culture for 2 to 3 wk. Cultured NK-2.1+ cells displayed a cell surface phenotype (Asialo-GM1+, Thy-1.2+, L3T4-, Lyt-2-) and lytic activity similar to that described for freshly isolated NK cells of normal mice. Furthermore, T cell receptor (TCR) genes of the TCR-gamma and TCR-beta loci were in germline configuration, and no functional transcripts of TCR-gamma, TCR-beta, or TCR-alpha were detected. We propose that the expression of the TCR is not necessary for functional NK activity, and NK cells are distinct from both mature cytotoxic T lymphocytes and the earliest identifiable T cells.
Induction, maintenance, and reinduction of tumoricidal activity in bone marrow-derived mononuclear phagocytes by Corynebacterium parvum. Evidence for the involvement of a T cell- and interferon-gamma-independent pathway of macrophage activation.
Authors: Keller R , Keist R , Van der Meide P H , Groscurth P , Aguet M , Leist T P 
Published: December 2022

Abstract
Rat bone marrow-derived mononuclear phagocytes, virtually homogeneous with respect to the cell lineage, do not exhibit spontaneous tumoricidal activity in the resting state. When incubated with macrophage-activating lymphokines, rat recombinant interferon-gamma (IFN), or heat-killed Corynebacterium parvum, bone marrow-derived mononuclear phagocytes readily evolve tumoricidal activity. Whereas tumoricidal activity induced by lymphokines and/or rat recombinant IFN-gamma is short-lived, that elicited by C. parvum is maintained for at least 2 wk, provided that the C. parvum organisms are continuously present in the culture. After washing off extracellular organisms, C. parvum-induced tumoricidal activity decays rapidly, suggesting that sustained extracellular stimulation is required for its maintenance. Induction of tumoricidal activity by macrophage-activating lymphokines and/or rat recombinant IFN-gamma is fully prevented by polyclonal and monoclonal anti-IFN-gamma antibodies; in contrast, induction by C. parvum is not affected by anti-IFN-gamma. Since induction of tumoricidal activity by C. parvum takes place irrespective of the presence of anti-Thy-1 antisera or cyclosporin A, T cells and/or their products appear not to be involved in this type of macrophage activation. Accordingly, present findings provide evidence for the existence of lymphokine-independent pathways of macrophage activation.
Functional maturation of murine B lymphocyte precursors. I. Selection of adherent cell-dependent precursors from bone marrow and fetal liver.
Authors: Gisler R H , Holländer G , Söderberg A 
Published: December 2022

Abstract
A cell culture assay is described which is suitable to explore interactions between cells of the bone marrow (BM) microenvironment on one side and B lymphocyte progenitors on the other. First, a heterogeneous adherent BM (aBM) cell population was established on Cytodex 1 microcarriers. Then, adherent cell and surface IgM+(sIgM+) cell-depleted BM precursors or adherent cell-depleted day 12 fetal liver cells were added. The generation of B cells in these cultures was monitored by staining with fluorochrome-labeled anti-mu-chain antibody and by lipopolysaccharide (LPS) induction of protein A plaque-forming cells at limiting dilution. In the absence of aBM cells, some B cells arose after 24 hr from BM precursors but not from day 12 fetal liver cells. With aBM cells, BM precursors gave rise to a distinct second wave of B cells starting after 5 days of culture. When fetal liver cells were cultured on aBM cells, B cells appeared after a delay of 4 to 5 days. By using Ig allotype-congenic mouse strains (C.AL 20, BALB/c) and an allotype-specific plaque assay, we established that mature B cells originate from the putative progenitors and not from the aBM cell population. In an attempt to eliminate the aBM cell-independent progenitor subset, mice were pretreated with 5-fluorouracil 5 days before BM cells were collected. The remaining cells still contained B cells, but the frequency of c mu+ sIgM- pre-B cells was less than 10(-5). Remaining B cells were removed by anti-mu panning. In cultures of this precursor cell population, LPS-responsive B cells appeared after a delay of about 1 wk, and their generation was totally aBM cell-dependent and was maintained for more than 2 wk.
Enhancement of a human antibody response in vitro mediated by interaction of interferon-alpha with T lymphocytes.
Authors: Evans S S , Ozer H 
Published: December 2022

Abstract
This study describes the effects of human recombinant IFN-alpha 2 on antibody production in vitro. Whereas the inclusion of IFN-alpha 2 in cultures for 7 days had a relatively minor effect on pokeweed mitogen (PWM)-induced antibody production, it resulted in a dose-related enhancement of a hapten-specific primary antibody response. Comparison of PWM and IFN-induced [3H]thymidine uptake indicated that the observed IFN activation was not polyclonal. Pretreatment of T cells with IFN for 1 hr before recombination with untreated autologous B lymphocytes increased the anti-TNP response four-fold, whereas similar pretreatment of B lymphocytes had no effect. Furthermore, 2000 R x-irradiation of T cells before coculture with autologous B lymphocytes and IFN abrogated the TNP-specific response. These results indicate that IFN modulates TNP-specific antibody production via a radiosensitive T-helper function. Further subfractionation by panning suggests that the enhancement is mediated by the Leu-3a+ helper/inducer T cell subset. Evidence that a 1-hr exposure to IFN was sufficient to modulate antibody production prompted the examination of T cells for possible receptor mechanisms. Scatchard analysis of 125I-IFN-alpha 2 binding revealed approximately 65 high affinity IFN receptors per cell with an apparent dissociation constant (Kd) of 4.4 X 10(-10) M. This paper is the first demonstration of the role of T cells in mediating the effects of recombinant IFN-alpha 2 on human primary antibody responses in vitro. These data further suggest that the observed modulation of hapten-specific antibody production in vitro by IFN may involve the binding of IFN to specific cellular receptors expressed by T lymphocytes.
Activation of glomerular mesangial cells by the terminal membrane attack complex of complement.
Authors: Lovett D H , Haensch G M , Goppelt M , Resch K , Gemsa D 
Published: December 2022

Abstract
Treatment of cultured renal glomerular mesangial cells (MC) with nonlytic concentrations of the purified components (C5b-9) of the terminal membrane attack complex (MAC) of complement induced significant functional alterations characteristic of cellular activation. C5b-9-treated MC released large quantities of primarily vasodilatory prostaglandins. In addition, the secretion of an MC-derived auto-growth factor (MC interleukin 1) was greatly enhanced. Examination of the action of C5b-9 on MC phospholipid metabolism indicated that complement induced the activation of phospholipases, leading to quantitative changes in the fatty acid profile of MC membrane phospholipids. These findings demonstrate that cultured MC are highly responsive to nonlytic concentrations of the C5b-9 complex, and suggest that the mesangial deposition of the MAC in many forms of glomerular disease, with resultant cellular activation, may play a major role in the hemodynamic and cellular proliferative events characteristic of these disorders.
Normal trophoblasts resist induction of class I HLA.
Authors: Hunt J S , Andrews G K , Wood G W 
Published: December 2022

Abstract
Very few types of normal cells fail entirely to express class I human leukocyte antigens (HLA), and many of those cells (sperm, fetal amnion epithelial cells, and fetal trophoblasts) are related to the process of reproduction. Susceptibility of sperm to modulation of class I antigens has not been examined, but it has recently been demonstrated that amnion cells respond to exposure to IFN-gamma with readily detectable levels of class I antigens. In addition, one of two trophoblast cell lines (BeWo) has been shown to exhibit enhanced expression of class I HLA in response to IFN-gamma. Expression by a second trophoblast cell line (Jar) was not inducible. Findings in the present study included demonstration of IFN-gamma-enhanced class I-specific mRNA synthesis in JEG-3 cells, which are derived from BeWo, and failure of synthesis by Jar cells. Those results eliminated trivial explanations for the preceding findings and confirmed the responsiveness of some but not all cells of trophoblast origin to IFN-gamma. When successful modulating conditions for amnion and malignant trophoblast cells were applied to normal tissues, third trimester term chorionic cytotrophoblasts and first trimester villous syncytial and cytotrophoblasts failed to exhibit class I HLA. Neither malignant nor normal trophoblasts expressed class II HLA under any condition of testing. Failure of induction of HLA expression by normal trophoblasts could not be attributed to either loss of viability by tissue explants or failure of modulating reagents to reach the trophoblasts. The results demonstrate that regulation of expression of histocompatibility antigens by major populations of normal trophoblasts and one of two choriocarcinoma cell lines differs markedly from that of other fetal and adult cells. Uncommon regulatory mechanisms may be essential to maintenance of the trophoblast as an immunologically inert barrier between the mother and her antigenically disparate fetus.
Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to Coxsackievirus B3-induced myocarditis.
Authors: Neu N , Beisel K W , Traystman M D , Rose N R , Craig S W 
Published: December 2022

Abstract
Several mouse strains are susceptible to immunopathic myocarditis after infection with Coxsackievirus B3 (CB3). This disease is associated with autoantibodies that are directed against myosin. In this study we characterized sera from CB3-infected mice for their reactivity with three different myosin isoforms (heart, skeletal muscle, and brain myosins) and for autoantibody isotype by using an ELISA. Competitive inhibition assays and absorption studies with various myosins demonstrated the presence of two autoantibody populations in sera of susceptible A.CA and A.SW mice. The first was specific for cardiac myosin and was mainly IgG. The second antibody population cross-reacted with heart, skeletal muscle, and brain myosin and was mainly IgM. B10.PL/SgSf and B10.A/SgSf mice, which do not develop immunopathic myocarditis, produced only the IgM autoantibody population cross-reactive with all three myosin isoforms. Because the heart-specific myosin autoantibodies were found exclusively in the mouse strains that developed immunopathic myocarditis, they can be considered a serologic marker for autoimmune heart disease.
In vitro evidence that carbohydrate moieties derived from uromodulin, an 85,000 dalton immunosuppressive glycoprotein isolated from human pregnancy urine, are immunosuppressive in the absence of intact protein.
Authors: Muchmore A V , Shifrin S , Decker J M 
Published: December 2022

Abstract
Our laboratory recently reported the purification of a unique immunosuppressive glycoprotein isolated from human pregnancy urine (7). This glycoprotein, which we term uromodulin, has a m.w. of 85,000 as assessed on SDS-PAGE and is 30% carbohydrate. Uromodulin blocks in vitro antigen-specific T cell proliferation to recall antigens such as tetanus toxoid at concentrations as low as 100 pM. This glycoprotein also blocks the in vitro generation of spontaneous monocyte-mediated cytotoxicity (7, 36). Recent evidence strongly suggests that the primary action of uromodulin is to act as a specific ligand and modulator of IL 1 (10, 33). We now report additional biochemical characterization of uromodulin, and based on three independent lines of evidence, find that its immunologic activity appears to result from its glycosylation. First, measures to alter the tertiary folding of the protein backbone of uromodulin, including succinylation or reduction and carboxymethylation, fail to significantly affect its in vitro bioactivity. Second, after extensive digestion of intact uromodulin with pronase, the majority of the in vitro bioactivity can be recovered in a single carbohydrate-rich fraction. Finally, digestion with N-glycanase (N-glycosidase F-, an enzyme specific for N-asparagine-linked oligosaccharides) and subsequent purification on thin layer chromatography yields a single complex oligosaccharide that appears to be responsible for the majority of the in vitro immunosuppression mediated by uromodulin. These data suggest that uromodulin displays N-linked carbohydrate sequences capable of down-regulating antigen-specific T cell responses in vitro. It has been suggested that endogenous lectins may play an important role as recognition molecules in mammalian, as well as more primitive immune systems (23, 24). Our in vitro biologic data strongly suggest that the carbohydrate portion of uromodulin is an excellent candidate to function as a potential lectin receptor.
Interactions between precipitating and nonprecipitating antibodies in the formation of immune complexes.
Authors: Cosio F G , Birmingham D J , Sexton D J , Hebert L A 
Published: December 2022

Abstract
In the present study, we used monoclonal antidinitrophenol (DNP) antibodies to determine certain of the biophysical characteristics of precipitating and nonprecipitating antibodies. In addition, we studied the dynamics of immune complex (IC) formation when precipitating antibodies react with antigen in the presence of nonprecipitating antibodies. The antigen utilized in these studies was DNP-bovine serum albumin. All isolated nonprecipitating anti-DNP antibodies were of the IgG2b isotype, whereas all antibodies with other isotypes (IgG1, IgG3, IgM, IgA and IgE) were precipitating. Nonprecipitating antibodies did not differ significantly from precipitating antibodies in affinity, valence, or isoelectric point. Nonprecipitating antibodies inhibited the formation of precipitable IC between antigen and precipitating antibodies. In addition, preformed IC precipitates were solubilized by nonprecipitating antibodies. The solubilization of IC precipitates was influenced by the isotype of the precipitating antibody and by the antibody:antigen ratio in the IC precipitate. By isokinetic sucrose density centrifugation, we determined that solubilization of IC precipitates by nonprecipitating antibodies was associated with release of free precipitating antibody and formation of soluble IC between the antigen and the nonprecipitating antibody. In conclusion, in this study the nonprecipitating property of mouse anti-DNP antibodies is isotype-specific. Nonprecipitating antibodies compete and displace precipitating antibodies from the antigen, resulting in inhibition of IC precipitation and in IC solubilization. On the basis of the present results, we postulate that antibody-antibody interactions are important determinants of precipitating ability, and that these interactions are a characteristic of antibody isotype.