bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed-type hypersensitivity in mast cell-deficient mice: dependence on platelets for expression of contact sensitivity.
Authors: Geba G P , Ptak W , Anderson G M , Paliwal V , Ratzlaff R E , Levin J , Askenase P W 
Published: December 2022

Abstract
Previous studies of cutaneous T cell-mediated responses in mice have obtained pharmacologic, morphologic, and immunologic evidence pointing to a critical role for local mast cells in release of the vasoactive amine serotonin (5-HT) to mediate early, initiating events that are required for elicitation of these responses. However, the role of mast cells in initiating these T cell-mediated cutaneous responses has been questioned due to the presence of relatively intact delayed-type hypersensitivity responses, such as contact sensitivity (CS), in mast cell-deficient mice whose skin contains only 1 % normal mast cell numbers. The contribution of other potential local sources of 5-HT, such as circulating platelets, at the site of a delayed-type hypersensitivity or CS response in these mast cell-deficient strains, has not been investigated. Therefore, we studied the effect of systemic platelet depletion, produced with an anti-platelet Ab, on blood and tissue levels of 5-HT, and on in vivo T cell-mediated cutaneous sensitivity responses, in W/Wv and Sl/Sld mast cell-deficient mice. The results showed that: 1) platelet depletion severely reduced whole blood 5-HT; 2) tissue levels of 5-HT, in mast cell-deficient mice, depended in large part on the presence of circulating platelets, and 3) specific depletion of platelets markedly suppressed CS responses in both W/Wv and Sl/Sld mast cell-deficient mice, and only moderately reduced CS in normal +/+ congenic mast cell-sufficient controls, but did not decrease CS in beige mice, with platelet granules that are defective in storage of 5-HT. We concluded that platelets may provide 5-HT crucial for the initiation of cutaneous T cell-mediated immune responses, such as CS.
Th1 development of naive CD4+ T cells is inhibited by co-activation with anti-CD4 monoclonal antibodies.
Authors: Goedert S , Germann T , Hoehn P , Koelsch S , Palm N , Rüde E , Schmitt E 
Published: December 2022

Abstract
Co-activation of CD4+ T cells by anti-CD4 mAb strongly enhances the proliferation of these T cells. We have analyzed the influence of CD4-mediated co-activation on Th cell differentiation. Our data demonstrate that activation of high density (HD)-CD4+ T cells by immobilized anti-CD3 mAb in combination with immobilized anti-CD4 mAb led to a strong inhibition of Th1 differentiation and to a variable but significant induction of Th2 development. Priming of highly enriched Mel-14highCD4+ T cells in the presence of anti-CD4 mAb also resulted in a pronounced suppression of secondary IFN-gamma production, indicating that the Th1 development of naive CD4+ T cells is inhibited by co-activation via CD4. In contrast to HD-CD4+ T cells, CD4-induced costimulation of MEL-14highCD4+ T cells did not result in a primary and secondary IL-4 production. Hence, these results suggest that a MEL-14low population within the HD-CD4+ T cell fraction was the source of the endogenous IL-4 and imply, in addition, that co-activation via CD4 inhibits the development of Th1 cells from naive CD4+ T cells independently from endogenous IL-4. This assumption is further corroborated by the fact that neither the application of neutralizing anti-IL-4 mAb nor the use of T cells from IL-4 knockout mice could prevent CD4-mediated inhibition of Th1 development. The Th1-inhibiting effect of anti-CD4 mAb could not be reversed by the application of the Th1 inducer IL-12. On the contrary, the secondary IL-4 production of HD-CD4+ T cells as an indicator of Th2 differentiation, which was promoted by anti-CD4 mAb, was enhanced even in the presence of IL-12. Therefore, our results suggest that co-activation of naive CD4+ T cells by anti-CD4 mAb directly and selectively inhibits Th1 differentiation of naive dense CD4+ T cells.
Bcmd governs recruitment of new B cells into the stable peripheral B cell pool in the A/WySnJ mouse.
Authors: Lentz V M , Cancro M P , Nashold F E , Hayes C E 
Published: December 2022

Abstract
The A/WySnJ mouse provides a genetic model for studying new B cell selection into the stable peripheral B cell pool. Unlike the related A/J strain, the A/WySnJ has a single, autosomal codominant gene defect, Bcmd, resulting in a profound peripheral B cell deficiency. Here, continuous in vivo bromodeoxyuridine labeling and immunofluorescence analysis showed normal bone marrow B cell genesis but excessive B cell loss from the marrow and each peripheral pool in A/WySnJ. The A/WySnJ immature B220low/HSAhigh splenic B cell pool was 79% smaller, had a 69% slower renewal rate, and its cells had a 29% shorter average half-life than A/J. The A/WySnJ mature B220high/HSAlow splenic B cell pool was 92% smaller, had an 83% slower renewal rate, and its cells had a 56% shorter average half-life. In reciprocal chimeras, the A/WySnJ marrow failed to repopulate the peripheral B cell pool in A/J mice, whereas the A/J marrow fully reconstituted the A/WySnJ mice. Histochemistry revealed disordered splenic architecture in A/WySnJ, with few primary lymphoid follicles and a second abnormal phenotype, mastocytosis. There was no common genetic basis for B cell deficiency and mastocytosis in the F2 progeny of an (A/WySnJ x CAST/Ei)F1 intercross. We conclude that Bcmd is expressed in bone marrow cells, most likely B cells, where it hinders short-lived B cell maturation to a long-lived phenotype with the potential to form memory B cells.
Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation.
Authors: Maurer D , Fiebiger S , Ebner C , Reininger B , Fischer G F , Wichlas S , Jouvin M H , Schmitt-Egenolf M , Kraft D , Kinet J P , Stingl G 
Published: December 2022

Abstract
Originally limited to basophils and mast cells, the spectrum of high affinity IgE receptor (Fc epsilon RI-bearing cells has expanded recently to include Langerhans cells, dermal dendritic cells (DC), monocytes, and eosinophils. As a result of studies on the distribution, structure, and function of Fc epsilon RI on APCs, we discovered a minor nonbasophil, nonmonocyte PBMC population that can bind IgE via Fc epsilon RI. This receptor occurs on the surface of these cells as a multimeric structure containing Fc epsilon RI alpha- and Fc epsilon RI gamma-chains but, unlike its counterpart on basophils, lacking Fc epsilon RI beta. Further experiments revealed that these Fc epsilon RI alpha gamma-expressing cells closely resemble peripheral blood DC by immunophenotype (HLA-DRhigh, HLA-DQhhigh; CD4+, CD11a+, CD32+, CD33+, B7/2 (CD86)+; CD11blow, CD14low, CD40low, CD54low, CD64low) and cell morphology. These features allowed us to isolate Fc epsilon RI-expressing DC from the peripheral blood and to investigate their immunostimulatory properties. We found Fc epsilon RI-positive DC to be efficient stimulators of both primary (allogeneic MLR) and Fc epsilon RI/IgE-dependent, secondary T cell responses at low cell numbers. Thus, Fc epsilon RI-expressing DC may not only amplify established type I allergic immune reactions but, unlike Fc epsilon RI-positive semiprofessional APCs, may be able to prime naive T cells to common and/or cryptic epitopes of IgE-reactive Ags.
IFN-gamma-induced MHC class II gene expression is suppressed in endothelial cells by dextran sulfate.
Authors: Lian R H , Kotwal G J , Wellhausen S R , Hunt L A , Justus D E 
Published: December 2022

Abstract
IFN-gamma-activated endothelial cells actively participate in initiating immune responses by interacting with immunocompetent cells via class II MHC proteins. In this study, dextran sulfate, a synthetic heparin analogue, was shown to selectively inhibit IFN-gamma-induced surface expression of HLA-DR molecules by human umbilical cord vascular endothelial cells, but not other cytokine-induced molecules such as ELAM-1 or ICAM-1. Inhibition occurred regardless of whether dextran sulfate was added 24 h before, at the same time as, or 24 h after IFN-gamma stimulation of cells. In addition, both high (500 kDa) and low (5 kDa) molecular mass dextran sulfate molecules were able to block class II expression, whereas treating cells with naturally occurring polysulfated glycosaminoglycans such as heparin, heparan, and chondroitin sulfate did not produce any suppressive effects. Radiolabeling of cells with [35S]methionine followed by radioimmunoprecipitation using anti-HLA-DR alpha mAb demonstrated that biosynthesis of class II proteins was specifically blocked. RT-PCR and Southern blotting were utilized to examine transcription of the HLA-DR alpha gene and demonstrated an absence of HLA-DR alpha mRNA from dextran sulfate-treated and IFN-gamma-induced cells. Dextran sulfate also prevented transcription of the gene encoding CIITA, a transactivator protein required for IFN-gamma-inducible expression of class II genes. Thus, dextran sulfate apparently inhibited this step or an earlier one in the intracellular signaling pathway for IFN-gamma in human endothelial cells, subsequent to IFN-gamma binding to its cell surface receptor.
Accelerated amyloid deposition in mice treated with the aspartic protease inhibitor, pepstatin.
Authors: Yamada T , Liepnieks J , Benson M D , Kluve-Beckerman B 
Published: December 2022

Abstract
The development of amyloidotic diseases is believed to be determined in large part by the structure and metabolism of the amyloid subunit protein. The amino-terminal region of serum amyloid A (SAA), the subunit precursor protein in reactive amyloidosis, appears to confer fibrillogenic potential. Here we present data consistent with the hypothesis that amyloid A fibrillogenesis is favored when proteolysis of the amino-terminal region of SAA is impaired. Murine tissue extracts were found to contain pepstatin-inhibitable protease activity that cleaved mouse SAA2 between Glu8 and Ala9. Tissues obtained from mice that had been treated with pepstatin for 3 days lacked this activity. To investigate a possible relationship between inhibition of aspartic proteases and amyloidogenesis, mice were treated with pepstatin while concurrently undergoing a standard amyloid induction protocol (repeated casein injections). Pepstatin-treated mice showed amyloid deposition significantly sooner than the control group, which had received only casein. During the preamyloidotic phase, pepstatin-treated mice had higher concentrations of SAA in serum and spleen than control mice. In addition, clearance of injected 125I-labeled SAA from plasma was significantly delayed. Based on these findings, it is reasonable to postulate that inhibition of aspartic protease activity can lead to an accumulation of amino-terminally intact SAA molecules and thereby accelerate amyloid fibril formation.
Analysis of the fine B cell specificity during the chronic/relapsing course of a multiple sclerosis-like disease in Lewis rats injected with the encephalitogenic myelin oligodendrocyte glycoprotein peptide 35-55.
Authors: Ichikawa M , Johns T G , Liu J , Bernard C C 
Published: December 2022

Abstract
We have recently shown that a single injection of myelin oligodendrocyte glycoprotein (MOG), or the MOG35-55 peptide, produces a relapsing-remitting neurologic disease with extensive plaque-like demyelination. Given the features that this new autoimmune demyelinating model has in common with the clinicopathologic manifestations of multiple sclerosis, we have examined the Ab reactivity to native MOG and MOG35-55 peptide during the course of the disease in Lewis rats. Following immunization with MOG35-55, varied clinical symptoms were observed; these included hind and foreleg paralysis and various degrees of balance impairment. Disease progression also varied: 3 out of 21 animals had a single mild disease episode; 4 out of 21 had a mild relapsing-remitting disease; and 14 out of 21 had severe relapsing-remitting disease. Ab reactivity to MOG35-55 and native MOG was first detected in all rats 4 wk postimmunization and persisted throughout the 12 wk of observation. The Ab response was highly restricted with no reactivity to other peptides encompassing different extracellular segments of MOG. Fine epitope mapping showed that Ab from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37-46 and to a lesser extent to MOG43-50. Although significant levels of anti-MOG Abs appeared necessary for the development of demyelinating lesions, their presence in blood and cerebrospinal fluid alone was not sufficient to produce severe clinical symptoms. These results demonstrate that the MOG35-55 peptide is highly encephalitogenic and can induce strong T and B cell responses. It is probably the complex interaction between these T and B cells that determines the severity of disease in individual rats.
Cloning and analysis of IgG kappa and IgG lambda anti-thyroglobulin autoantibodies from a patient with Hashimoto's thyroiditis: evidence for in vivo antigen-driven repertoire selection.
Authors: McIntosh R S , Asghar M S , Watson P F , Kemp E H , Weetman A P 
Published: December 2022

Abstract
Antibodies to thyroglobulin (Tg) are commonly found in patients with the autoimmune thyroid diseases Graves' disease and Hashimoto's thyroiditis as well as in individuals with apparently normal thyroid function. Although it is not clear how Tg Abs are involved in the pathology of the diseases, the study and analysis of these Abs may nevertheless be instructive in allowing the development of an Ab response to an autoimmune disease-associated self Ag to be followed. We have prepared IgG kappa and lambda phage display combinatorial libraries from the cervical lymph node of a single Hashimoto's thyroiditis patient with a high anti-Tg titer. These were selected with purified human Tg, and 10 IgG kappa and 9 IgG lambda clones were analyzed further. Sequence analysis of the clones showed a very highly restricted heavy chain usage and a less restricted light chain usage. There was a variable degree of divergence from germ-line sequence in the light chain sequences, with a clear relationship between relatively higher affinity of the Fab for human Tg and an increased degree of somatic hypermutation. The Tg-selected Fab did not bind to Tg from other species, to reduced denatured Tg, or to thyroid peroxidase. The Fab inhibited patient serum binding to human Tg by between 39 and 79%. In summary, we have isolated 19 high affinity, human Tg-specific Fab and shown that the relative affinity of the Fab is directly related to the pattern of somatic hypermutation.
Different CD40-mediated signaling events require distinct CD40 structural features.
Authors: Hostager B S , Hsing Y , Harms D E , Bishop G A 
Published: December 2022

Abstract
Signals delivered to B cells through CD40 are critical to the development of humoral immune responses. In this study we characterize regions of the 62-amino acid cytoplasmic domain of human CD40 (hCD40) that are essential for signal transduction and examine the functional consequences of mutations in these regions. A panel of mutant hCD40 molecules was stably expressed in mouse B cell lines and tested for its ability to stimulate Ab secretion, homotypic adhesion, and increased surface expression of B7, Fas, CD23, LFA-1, and intracellular adhesion molecule-1. Our results indicate that CD40 contains at least two major signaling determinants in the cytoplasmic domain: one disrupted by a truncation of 22 amino acids, and a second disrupted by the removal of 10 additional amino acids. The second determinant includes threonine 234, a residue previously shown to be important in CD40 signal transduction. Our functional analysis of alanine and serine substitutions at position 234 indicates that phosphorylation of this residue may be important for full CD40 signaling activity.
Cyclic adenosine 3',5'-monophosphate increases the open probability of potassium channels in activated human T cells.
Authors: Oleson D R , DeFelice L J , Quinn M F , Donahoe R M 
Published: December 2022

Abstract
In the present report we describe a cAMP-responsive K channel in activated human T cells. Single channel events were recorded using the patch-clamp technique in cell-attached-patch configuration. The channel was K selective, as determined by reversal potentials under different K gradients, and displayed voltage-independent gating. When the applied potential (Vp) was equal to zero, the conductance of the channel was 21.8 +/- 0.9 pS with 150 mM K in the electrode. Typical patches contained between two and seven channels that were relatively quiet, or silent, before agonist stimulation. Adenosine (20-30 microM) increased the average open time probability from 0.017 +/- 0.008 to 0.108 +/- 0.054 over a period of 108 s. Subsequent addition of the phosphodiesterase inhibitor Ro 20-1724 (0.5 mM) increased the probability of being in the open state to 1.155 +/- 0.407 over a period of 180 s. Channel kinetics were well described by assuming two open and two closed states. Exponential time constants for the open states were 0.51 +/- 0.06 and 4.34 +/- 0.31 ms, and closed state time constants were 0.58 +/- 0.05 and 10.1 3 +/- 2.32 ms. In addition, extracellular ATP (0.3-1.0 mM) decreased channel activity. Moreover, Rp-cAMP (0.5-1.0 mM), an antagonist that specifically blocks the ability of cAMP to bind and activate protein kinase A, failed to inhibit adenosine- and Ro 20-1724-induced increases in channel activity, implying a direct action of cAMP on channel gating.
Identification of a novel regulatory region critical for expression of the RANTES chemokine in activated T lymphocytes.
Authors: Nelson P J , Ortiz B D , Pattison J M , Krensky A M 
Published: December 2022

Abstract
The RANTES chemokine is a T cell-expressed, proinflammatory cytokine recently implicated as a suppressive agent of HIV replication. We have identified tandem kappaB-like sequences within the promoter for RANTES that are critical for RANTES promoter-reporter gene activity in both the T cell tumor line Hut78 and in PHA-activated PBL. This region binds not only Rel family members (including p50-p65 heterodimers and p50-p50 homodimers) but also non-Rel factors up-regulated in PBL 3 to 5 days following activation. The expression of these "late" expressed nuclear factors correlates with an up-regulation of RANTES message found at this point in T cell activation. These factors are also constitutively expressed in functionally mature CD8+ T cells. We hypothesize that these apparently novel proteins are responsible in part for the temporal regulation of RANTES seen in peripheral blood T cells and represent a component of transcriptional regulatory machinery newly expressed at this "late" stage of peripheral T cell development.
Differential regulation of c-Rel translocation in activated B and T cells.
Authors: Venkataraman L , Wang W , Sen R 
Published: December 2022

Abstract
c-Rel induction in activated lymphocytes is suppressed by the immunosuppressive drug, FK506. Here we show that FK506-suppressible, delayed c-Rel induction is similar in B and T cells and is regulated by mRNA production. In contrast, rapid nuclear translocation of pre-existing cytoplasmic c-Rel occurs only in B cells, but not in T cells. Analysis of I-kappaBalpha and -beta in these cells showed that both I-kappaBalpha and I-kappaBbeta were rapidly degraded in response to stimulation in B cells, but only I-kappaBalpha was affected in T cells. These observations suggest that 1) different Rel proteins in the same cell may be sequestered in the cytoplasm differently, 2) the sequestration mechanism is cell-type specific, and 3) differential sensitivities of I-kappaBalpha and beta in B and T cells may regulate, in part, the rapid response of family members. We propose that subunit-specific and cell-specific regulation of nuclear translocation may help determine the varied cellular responses to different stimuli.
Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine.
Authors: Tian J H , Miller L H , Kaslow D C , Ahlers J , Good M F , Alling D W , Berzofsky J A , Kumar S 
Published: December 2022

Abstract
The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.
TNF-alpha bidirectionally modulates the viability of primitive murine hematopoietic progenitor cells in vitro.
Authors: Jacobsen F W , Veiby O P , Stokke T , Jacobsen S E 
Published: December 2022

Abstract
It is well established that TNF-alpha can induce apoptosis in many normal and transformed cell types. The effects of TNF-alpha on cytokine-induced proliferation and differentiation of normal hematopoietic progenitors have been characterized extensively, whereas little is known about how TNF-alpha can affect their viability. The present studies suggest, based on experiments using delayed addition of growth-promoting cytokines as well direct viability assays, that TNF-alpha bidirectionally affects the survival of individually cultured primitive Lin- Sca-1+ hematopoietic progenitors, in that stem cell factor (SCF)-, granulocyte-CSF-, IL-6-, and IL-11-induced survival is potently counteracted by TNF-alpha (42-86%), whereas TNF-alpha synergistically enhances IL-1alpha-induced survival up to threefold. The bidirectional effects of TNF-alpha on hematopoietic growth factor-induced survival of hematopoietic progenitors were reflected in that TNF-alpha enhanced apoptosis of Lin- Sca-1+ cells when combined with SCF, whereas TNF-alpha synergistically suppressed apoptosis in response to IL-1alpha.