bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ig-binding bacterial proteins also bind proteinase inhibitors.
Authors: Sjöbring U , Trojnar J , Grubb A , Akerström B , Björck L 
Published: December 2022

Abstract
Protein G is a streptococcal cell wall protein with separate binding sites for IgG and human serum albumin (HSA). In the present work it was demonstrated that alpha 2-macroglobulin (alpha 2M) and kininogen, two proteinase inhibitors of human plasma, bound to protein G, whereas 23 other human proteins showed no affinity. alpha 2M was found to interact with the IgG-binding domains of protein G, and in excess alpha 2M inhibited IgG binding and vice versa. A synthetic peptide, corresponding to one of the homologous IgG-binding domains of protein G, blocked binding of protein G to alpha 2M. Protein G showed affinity for both native and proteinase complexed alpha 2M but did not bind to the reduced form of alpha 2M, or to the C-terminal domain of the protein known to interact with alpha 2M receptors on macrophages. Binding of protein G to alpha 2M and kininogen did not interfere with their inhibitory activity on proteinases, and the interaction between protein G and the two proteinase inhibitors was not due to proteolytic activity of protein G. The finding that protein G has affinity for proteinase inhibitors was generalized to comprise also other Ig binding bacterial proteins. Thus, alpha 2M and kininogen, were shown to bind both protein A of Staphylococcus aureus and protein L of Peptococcus magnus. The results described above suggest that Ig-binding proteins are involved in proteolytic events, which adds a new and perhaps functional aspect to these molecules.
Identification and characterization of T helper epitopes in the nucleoprotein of influenza A virus.
Authors: Gao X M , Liew F Y , Tite J P 
Published: December 2022

Abstract
By using a series of overlapping synthetic peptides that cover more than 95% of the amino acid sequence of nucleoprotein (NP) of influenza A/NT/60/68 virus, five Th cell epitopes in B10.S (H-2s), BALB/c (H-2d), CBA (H-2k), and B6 (H-2b) mice have been identified. The specificity of Th cell recognition of epitopes is largely dependent on the H-2 haplotype of the responding mouse strain. However, two out of the five Th epitopes defined could be recognized by mice of more than one haplotype, implying that the primary sequence of protein antigens could also influence the selection of dominant T cell epitopes by the immune system. Immunization of B10.S mice with peptide 260-283 generated strong Th cell response against type A influenza viruses. In the other three strains of mice tested, priming with helper peptides induced a stronger antipeptide than antiviral T cell response. However, the low responsiveness to virus in these mice could be partially overcome by immunization with a mixture of several helper peptides. The Th epitopes are defined by the ability of the peptides to stimulate class II MHC restricted CD4+ T cells to proliferate and to produce IL-2 in vitro. When compared with the known epitopes on NP recognised by class I restricted CD8+ cytotoxic T cells, it appears that Th and cytotoxic T cell epitopes are nonoverlapping. The AMPHI and Motifs methods were employed to analyze the sequence of NP and predict the potential dominant sites in the molecule. The predictions are compared with the experimental data obtained and the implications discussed.
HLA-DRB1 and -DRB4 genes are differentially regulated at the transcriptional level.
Authors: Stunz L L , Karr R W , Anderson R A 
Published: December 2022

Abstract
The mechanism regulating the differential expression of DR beta 1 and DR beta 4 proteins on the surfaces of cultured EBV-transformed DR7 cell lines was investigated at the level of gene transcription. Steady-state levels of mRNA coding for DR7 beta 1 and DR beta 4 proteins were evaluated with the use of locus-specific oligonucleotide probes and relative transcriptional activity at the DR7B1 and DRB4 gene loci was measured with nuclear run-on transcription assays. Steady-state levels of DR7B1 mRNA were found to be three- to nine-fold higher than those of DRB4 in DR7,Dw7 cell lines, but no mature steady-state DRB4 mRNA was detectable in a DR7,Dw11 cell line which shows no detectable DR beta 4 protein. Run-on transcription assays performed with nuclei isolated from DR7,Dw7 cells showed a five-fold excess of DRB1 over DRB4 transcriptional activity, but, surprisingly, no difference in activity at the two DRB loci in nuclei isolated from DR7,Dw11 cells. Both DRB mRNA were quite stable as indicated by actinomycin D time course experiments. Thus the differential expression of the DR7 beta 1 and DR beta 4 proteins in the DR7,Dw7 cell lines arises at the level of mRNA production; the lack of detectable DR beta 4 protein in the DR7,Dw11 cell line, however, appears to be due to a different mechanism in which transcribed DRB4 sequences fail to be processed into mature mRNA molecules.
IL-5 up-regulates but IL-4 down-regulates IL-2R expression on a cloned B lymphoma line.
Authors: Yoshimoto T , Nakanishi K , Matsui K , Hirose S , Hiroishi K , Tanaka T , Hada T , Hamaoka T , Higashino K 
Published: December 2022

Abstract
Both IL-4 and IL-5 demonstrate B cell growth activity. IL-5 can render a cloned neoplastic B cell line, BCL1-CL-3 cells, responsive to IL-2, whereas IL-4 has no such activity. The response to IL-5 and IL-2 proceeds in two phases: the first phase which clearly depends upon IL-5 is the obvious increase in number of high affinity IL-2R (3.1-fold) with modest increase of low affinity IL-2R (1.2-fold) and gain of the ability of facilitated IL-2-binding and internalization of IL-2, and the second phase which is induced by IL-2 in the IL-5-stimulated CL-3 cells comprises the striking increase of low affinity IL-2R (8.5-fold). Kinetic study has revealed that high affinity IL-2R expressed on CL-3 cells begins to increase at 6 h and reaches to maximum at 12 h after stimulation with IL-5 or IL-5 plus IL-2, whereas low affinity IL-2R expression increases at 18 h and becomes maximal at 24 h after stimulation of CL-3 cells with IL-5 and IL-2. However, in the presence of IL-4, IL-5 cannot induce an increase in number of high affinity IL-2R on CL-3 cells. Thus, CL-3 cells stimulated with the mixture of IL-5 and IL-4 cannot respond to IL-2, and fail to show up-regulated expression of low affinity IL-2R. IL-4 also has a capacity to modestly interfere with the action of IL-2 to up-regulate low affinity IL-2R expression on IL-5-pretreated CL-3 cells. Thus, this monoclonal B cell system provides an excellent model system to define the roles of IL-5 and IL-4 involved in the B cell differentiation and to characterize the properties of B cells competent to IL-2 stimulation and the signal transduction mechanism which operates through IL-2/IL-2R system.
Tissue-specific expression of allogeneic class II MHC molecules induces neither tissue rejection nor clonal inactivation of alloreactive T cells.
Authors: Miller J , Daitch L , Rath S , Selsing E 
Published: December 2022

Abstract
To analyze the control of self tolerance to tissue-specific Ag, we have constructed C57BL/6 (H-2b) transgenic mice that express allogeneic class II (I-Ad) molecules exclusively on pancreatic islet cells. By a number of criteria, including I-Ad mRNA, and tissue and cell surface I-Ad protein levels, the islet cells appear to be expressing levels of I-Ad similar to B lymphocytes. Although one of the transgenic lines that expresses only the beta-chain occasionally displays slightly elevated glucose levels, this hyperglycemia is not enhanced when alpha and beta are coexpressed, allowing for cell surface I-Ad expression. None of the mice examined has demonstrated any autoimmune reaction to the I-Ad+ islet cells. Despite this apparent lack of recognition of the I-Ad+ islet cells, these animals demonstrate no reduction in the in vitro MLR generated to the same MHC molecule. Therefore, these mice remain functionally tolerant to the transgene product without inactivating those T cells that can recognize this same MHC molecule in vitro.
Regulation of the anti-alpha(1----3) dextran IgG antibody response of BALB/c mice by idiotype-specific T suppressor lymphocytes.
Authors: Stäb F , Austrup F , Kölsch E 
Published: December 2022

Abstract
The immune response of BALB/c mice against the so-called thymus-independent bacterial Ag alpha(1----3) dextran (Dex) is restricted to the expression of few major idiotypes (Id). It is furthermore under the control of T lymphocytes which regulate the isotype expression in such a way that they prevent anti-Dex IgG antibody production upon immunization. At the same time these T cells are part of a regulatory system for Dex-specific B cell memory formation. The underlying Ts cell activity has previously been analyzed by using euthymic and athymic congenic animals. Now we have isolated CD4-positive Id-specific T cell lines and clones which by several criteria are representatives of the above Ts cells. They inhibit in vitro proliferation and antibody secretion of Dex-specific hybridoma B cells. They prevent Id-restricted in vivo IgG anti-Dex antibody formation in T cell-reconstituted BALB/c nu/nu mice. At the same time they enforce, again Id-specific, accumulation of Dex-specific B memory cells. As has been shown previously under the influence of splenic Ts cells, these B memory cells are arrested in the original host but can be expanded and activated for anti-Dex IgG antibody formation upon adoptive transfer into X-irradiated allotype congenic nonresponder BALB.Ighb mice. The data show that the regulatory influence of T cells on the anti-Dex response is Id specific. It can now be studied by means of cloned Ts cells.
In situ localization of CD45 isoforms in the human thymus indicates a medullary location for the thymic generative lineage.
Authors: Gillitzer R , Pilarski L M 
Published: December 2022

Abstract
Previous work has suggested that the generative lineage within the human thymus can be defined by the selective expression of CD45 isoforms and is CD45RO- and predominantly CD45RA+. In order to physically localize these cells we have stained frozen sections of human thymus with antibodies to CD45RO (p180), and CD45RA (p205/P220), as well as with CD1 and HLA class I to define cortical and medullary areas, respectively. In the cortex, 70 to 90% of thymocytes were CD45RO+, whereas only 0.5% expressed CD45RA. Medullary cells were 30% CD45RO+, 29% CD45RA+; approximately 40% did not express detectable levels of either isoform but did express CD45 common determinants. To assess the degree of proliferation of cells expressing CD45 isoforms, we stained adjacent sections, or used double staining, with Ki67, an antibody that detects a nuclear Ag on proliferating cells. We found that CD45RA+ thymocytes are predominantly a resting medullary population with a small component in cell cycle, consistent with our analysis of human thymocytes by immunofluorescence, and with data in murine systems defining the generative lineage. To confirm that the CD1- or low, CD45RO-CD45RA+ thymocytes defined by immunofluorescence analysis were likely to have a medullary location, we analyzed the CD4/CD8 subset distribution of CD1-cells. From 80 to 90% of CD1-thymocytes are CD4+ or CD8+ single positives or CD-8- double negatives. CD1-thymocytes also include 12 to 14% CD4+8+ cells with a probable medullary location. A similar analysis of lymphocytes expressing a high density of HLA class I, which have a medullary location, confirmed the existence of CD4+8+ thymocytes in the medulla. Purified CD3-4-8- cells, previously shown to be CD1-CD45RA+, were also shown to bear a high density of HLA class I, indicating a medullary location. Correlative localization of a panel of Ag thus supports the argument for a medullary location of the thymic generative lineage.
Murine interstitial nephritis. IX. Induction of the nephritogenic effector T cell repertoire with an antigen-specific T cell cytokine.
Authors: Hines W H , Mann R A , Kelly C J , Neilson E G 
Published: December 2022

Abstract
The experiments presented in this report describe the biochemical and functional characteristics of a soluble Th cell factor (ThF) which can induce a nephritogenic effector T cell repertoire producing autoimmune interstitial nephritis. The ThF is Ag-specific, I-A-restricted, and comprises two chains noncovalently linked as a heterodimer. One chain at approximately 78,000 Mr is related to the TCR/Id and expresses a framework determinant (14-30) common to Ag-binding factors, and the other chain at approximately 82,000 Mr is I-A+. Together these chains can replace their parent cell by providing cognate help to precursor effector T lymphocytes in the presence of accessory cells, tubular Ag, and IL-2.
An intracellular calcium increase and protein kinase C activation fail to initiate T cell proliferation in the absence of a costimulatory signal.
Authors: Mueller D L , Jenkins M K , Chiodetti L , Schwartz R H 
Published: December 2022

Abstract
Resting T lymphocytes proliferate in response to a combination of a calcium ionophore and a phorbol ester. This observation suggests that an increase in intracellular calcium free ion concentration [Ca2+]i and activation of protein kinase C (PKC) are sufficient signaling events for the initiation of T cell proliferation. In contrast, an accessory cell-generated costimulatory signal, acting independently of the rise in [Ca2+]i and PKC activation, is required for Ag-induced proliferation of type I T cell clones. We now report that this costimulatory signal is unexpectedly also being delivered via a cell-cell interaction during the response to ionomycin and phorbol ester. In the absence of this signal (at limiting cell numbers), T cells fail to divide. We also demonstrate that proliferation in response to immobilized anti-CD3 mAb requires the cell-cell interaction. These results suggest a model of T cell stimulation in which activation of a costimulatory signaling pathway is important in the regulation of the IL-2 gene, and only in the presence of this (third) signal can an increase in [Ca2+]i and PKC activity induce T cell proliferation. Such a model predicts that IL-2-dependent expansion of T cell clones in vivo in response to Ag receptor occupancy requires the delivery of an independent accessory cell-derived co-stimulatory signal.
IL-1 beta modulation of spontaneous autoimmune diabetes and thyroiditis in the BB rat.
Authors: Wilson C A , Jacobs C , Baker P , Baskin D G , Dower S , Lernmark A , Toivola B , Vertrees S , Wilson D 
Published: December 2022

Abstract
Long term effects of in vivo treatment with human rIL-1 beta on diabetogenesis and thyroid disease were determined in the Biobreeding rat. Administration of high dose (10 micrograms/kg) IL-1 beta accelerated the onset of insulin-dependent diabetes mellitus compared to saline-injected controls. High dose treatment resulted in goiter development, pronounced LT, reduced serum T4 levels, and overall growth reduction. In contrast, low dose IL-1 beta (0.5 microgram/kg) administration significantly reduced the frequency of insulin-dependent diabetes mellitus (48%) compared to placebo (86%) and high dose IL-1 beta (93%) treatment groups. Rats protected by low dose IL-1 beta had unaffected growth rates and minimal to no pancreatic and thyroid pathology. Our results demonstrate that exogenous administration of IL-1 beta modulates Biobreeding rat idiopathic autoimmune diabetes and thyroid disease in a dose-dependent manner.
Production of hemopoietic colony-stimulating factors by astrocytes.
Authors: Malipiero U V , Frei K , Fontana A 
Published: December 2022

Abstract
Astrocytes may play a central role in regulation of immune mediated processes in the central nervous system. By their inducible expression of MHC class II Ag and secretion of cytokines they may propagate expansion and activation of T and B lymphocytes invading the brain tissue. Here we report that astrocytes may also contribute to the macrophage response observed in inflammatory and degenerative diseases of the brain. Murine astrocytes secrete granulocyte-macrophage CSF (GM-CSF) as evidenced by induction of colony formation in bone marrow cells and growth of FDC-P1 cells. Both effects are neutralized with anti-GM-CSF- but not with anti-IL-3-antibodies. Some residual activity detected in the bone marrow assay after antibody treatment can be explained by concomitant production of granulocyte CSF (G-CSF). The mRNA of both G- and GM-CSF are identified by Northern blots in astrocytes. Furthermore, mRNA for IL-1 alpha and IL-1 beta are detected in comparable amounts in astrocytes and brain macrophages, the latter, however, comprising much more potent sources of TNF-alpha.
Superoxide responses of immune complex-stimulated rat alveolar macrophages. Intracellular calcium and priming.
Authors: Hagenlocker B E , Walker B A , Ward P A 
Published: December 2022

Abstract
ATP is known to induce calcium transients in rat and human neutrophils and to "prime" these cells for enhanced oxygen radical responses after stimulation with chemotactic peptide, FMLP, or immune complexes. Calcium ionophores are also well known for their ability to prime phagocytic cells. In the current studies, nonelicited rat alveolar macrophages were analyzed for the ability of ATP as well as FMLP, C5a, platelet-activating factor and calcium ionophore (A23187) to modify levels of intracellular calcium and to enhance superoxide anion (O2-) production in response to immune complexes. Although none of these agents induced a O2- response under the conditions employed, all, except FMLP and C5a (human, recombinant) increased intracellular calcium, although the temporal features of the increases varied with the agent. In contrast to the inability of FMLP and C5a to cause intracellular calcium increases in macrophages, these same peptides caused dose-dependent intracellular calcium increases in rat neutrophils, whether the cells were derived from the blood or from the peritoneal cavity. On the basis of the effects of EGTA, the calcium increases in alveolar macrophages were caused by intracellular release of calcium in addition to some influx of extracellular calcium. Although ATP caused a dose-related increase in the level of intracellular calcium in alveolar macrophages, the cells were not "primed" for enhanced O2- responses to immune complexes. In contrast, platelet-activating factor and A23187, each of which induced increased intracellular levels of calcium, were able to prime macrophages for enhanced O2- responses. C5a and FMLP neither increased intracellular calcium levels nor primed macrophages for enhanced O2- responses to immune complexes. It is not clear if the inability of ATP to prime alveolar macrophages is caused entirely by insufficient increases in intracellular calcium or if ATP is unable to bring about additional changes that are relevant to the priming phenomenon.
Inhibition of antigen-induced airway hyperresponsiveness, but not acute hypoxia nor airway eosinophilia, by an antagonist of platelet-activating factor.
Authors: Ishida K , Thomson R J , Beattie L L , Wiggs B , Schellenberg R R 
Published: December 2022

Abstract
The role of platelet-activating factor (PAF) in Ag-induced airway hyperresponsiveness was evaluated in a guinea pig model using the PAF antagonist SDZ 64-412. Repeated OVA challenge by aerosol (twice weekly x 4 wk) of previously sensitized guinea pigs produced striking airway hyperresponsiveness as determined by pulmonary resistance changes to increasing doses of inhaled acetylcholine given 3 days after the last OVA challenge. Each OVA challenge produced significant hypoxia that was unaffected by oral pretreatment with 20 mg/kg SDZ 64-412, 2 h before each challenge (pO2 = 35 +/- 2 mm Hg for OVA alone vs 40 +/- 6 mm Hg for SDZ and OVA groups, respectively). SDZ 64-412 pretreatment abolished the airway hyperresponsiveness resulting from repeated Ag challenge. Morphometric analysis revealed that SDZ 64-412 treatment had no effect on the increased numbers of eosinophils that infiltrated the airways of OVA-challenged guinea pigs. These results suggest that PAF may be a primary mediator of airway hyperresponsiveness, but not acute bronchoconstriction, induced by repeated Ag challenge. This activity of PAF appears independent of eosinophil recruitment to airways.
Fluctuations in subsets of splenocytes and isotypes of Ig in young adult and aged mice resulting from Trypanosoma musculi infections.
Authors: Albright J W , Holmes K L , Albright J F 
Published: December 2022

Abstract
A prominent feature of parasitic infections is the marked hyperplasia of lymphoid tissues. The resultant disruption of those tissues may be a major cause of the immunodepression that typifies parasitic infections. Trypanosoma musculi infections in mice evoke lymphoid hyperplasia and depressed immune responses. T. musculi infections are more severe in C3H than in C57BL/6 (B6) mice; and more severe in aged mice of either strain, compared with young adults. This report concerns a flow cytometric analysis of splenic leukocytes, identified by various surface Ag, in young and aged, trypanosome-infected mice of C3H and B6 strains. Companion studies included quantification of serum Ig isotypes at intervals during infection. The results support the following conclusions: a) all major types of splenic leukocytes were activated by trypanosome infection resulting in enlargement of the cells and proliferation ("blastogenic response"); b) in all young-adult mice and in aged B6 mice (but not aged C3H mice) Thy-1+, Ly-1+, and Ly-4+ cells increased moderately during infection whereas the number of Ly-2+ cells remained constant; c) all cells of the B lineage increased during the course of infection (except in aged C3H mice) with disproportionate increases in the most mature stage (IgG+); d) the responses of young adult C3H and B6 mice to infection differed as illustrated by the ability of B6, but not C3H, mice to limit hyperplasia and reverse the effect; e) aging of B6 mice was reflected by relative inability to regulate generation of mature Ig-producing cells; f) aging of C3H mice was severe as reflected by the relative inability of most subsets of leukocytes to react to the infection, possibly because of abnormalities that were intrinsic in aged, normal C3H mice. It is likely that: a) disruption of lymphoid tissue, probably mediated by alterations in the production of and responsiveness to cytokines, is responsible for the depressed ability of the immune system to defend against parasites; and b) such disruptive effects, being more pronounced in aged animals and less easily brought under control, account for the greater vulnerability of aged animals to parasitic infection.