bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of IL-15 receptor alpha-chains on human peripheral blood mononuclear cells and effect of immunosuppressive drugs on receptor expression.
Authors: Chae D W , Nosaka Y , Strom T B , Maslinski W 
Published: December 2022

Abstract
IL-15, a newly described cytokine exerting IL-2-like in vitro activities, binds to and induces proliferation of cells co-expressing IL-15R alpha, IL-2R beta, and IL-2R gamma chains. To study the expression of human IL-15R alpha chains, we have utilized tagged human IL-15 protein and FACS analysis. In contrast to resting cells, mitogen-activated macrophages, NK cells, and CD4+ and CD8+ T cells express IL-15R alpha chains. Neither IL-2R alpha nor IL-2R beta chains are required for IL-15 binding. Dexamethasone, but not cyclosporine or rapamycin, blocks mitogen-induced IL-15R alpha expression. Dexamethasone-pretreated cells respond to IL-15 poorly, while the response to IL-2 is not affected. Thus, despite structural and functional similarities between IL-2R alpha and IL-15R alpha chains, the activation-triggered mechanisms of induction are different. Since IL-15R alpha chain is necessary and sufficient for IL-15 binding, regulation of IL-15R alpha expression may represent a new target for T cell-directed pharmacologic intervention.
Exposure to T helper 2 cytokines in vivo before encounter with antigen selects for T helper subsets via alterations in antigen-presenting cell function.
Authors: Cua D J , Coffman R L , Stohlman S A 
Published: December 2022

Abstract
The Th1 subset of CD4+ T cells mediate both delayed-type hypersensitivity (DTH) responses and experimental allergic encephalomyelitis (EAE). Th1 cells are induced by immunization of young adult female and older (&gt; or = 10 wk of age) male SJL mice. By contrast, young adult (&lt; or = 8 wk of age) male mice are characterized by the inability of immunization to induce either a DTH response or EAE, demonstrating a clear sex and age dependence to these Th1-mediated responses in SJL mice. T cell activation in age-matched female and male SJL mice was compared to understand the mechanism(s) of these differential responses. Here, we report that immunization of DTH responder female mice primes for Ag-specific secretion of IFN-gamma but not IL-4 and IL-10. In contrast, immunization of DTH nonresponder male mice primes Ag-specific T cells that secrete IL-4 and IL-10, but not IFN-gamma. Depletion of either IL-4 or IL-10 recovers DTH responsiveness in young adult male mice, demonstrating expansion of Th1 cells in these mice when Th2 cytokines are suppressed. The age- and sex-dependent inability to prime Th1 cells in young male mice is due to the functional absence of a macrophage APC population defined by co-expression of Mac-1 and Mac-3. To determine whether Th2 cytokines directly affect the APC's ability to support the priming of Th1 cells, Mac-3+ APC isolated from naive young male donors, which had been depleted of either IL-4 or IL-10, were transferred into DTH nonresponder males. Induction of DTH responses in these recipients demonstrates that in vivo suppression of Th2 cytokines enables the male-derived Mac-3+ APC to support priming of Th1 responses. These data indicate that, in addition to their regulatory roles in controlling preferential T cell subset expansion, exposure of APC to cytokines in vivo before the initial encounter with Ag may regulate induction of CD4+ T cell subsets.
The flt3 ligand promotes the survival of primitive hemopoietic progenitor cells with myeloid as well as B lymphoid potential. Suppression of apoptosis and counteraction by TNF-alpha and TGF-beta.
Authors: Veiby O P , Jacobsen F W , Cui L , Lyman S D , Jacobsen S E 
Published: December 2022

Abstract
The recently cloned fIt3 ligand (FL) potently enhances hemopoietic growth factor-induced growth of primitive hemopoietic progenitors. In agreement with previous reports, we found FL alone to be a weak mitogen for primitive Lin-Sca-1+ murine bone marrow progenitors. Using delayed addition of growth-promoting cytokines, we demonstrate that FL potently promotes the in vitro survival of Lin-Sca-1+ progenitors responsive to a potent myeloid growth factor combination (FL, stem cell factor (SCF), granulocyte CSF (G-CSF), and IL-1 alpha). Whereas no such progenitors survived in cultures supplemented with medium alone, 33% survived in FL compared with 75 and 13% in the presence of SCF and IL-1 alpha, respectively. These results were obtained when cells were plated individually, suggesting that the viability-promoting effect of FL is mediated directly on the progenitors. Whereas SCF was superior to FL in promoting the survival of FL-, SCF-, G-CSF-, and IL-1 alpha-stimulated Lin-Sca-1+ progenitors, FL was more efficient than SCF at promoting the survival of progenitors with a B cell potential, as measured by their ability to produce B220+ cells in response to delayed addition of FL, SCF, and IL-7. Seventy-one percent of the B220+ cell production could be recovered following 40-h incubation with FL compared with 2% in response to SCF. Analysis of day 12 spleen CFU content after 40-h preincubation of Lin-Sca-1+ cells in FL or SCF demonstrated that SCF maintained 64% of the day 12 spleen CFU, whereas only 16% survived in the presence of FL. Finally, there was no significant difference between the ability of FL and SCF to maintain the viability of long-term culture-initiating cells (25 and 32%, respectively). The ability of FL to promote the survival of Lin-Sca-1+ progenitor cells was reflected by the finding that FL also suppressed apoptosis. Finally, TGF-beta abrogated and TNF-alpha potently counteracted the survival-promoting effect of FL. Thus, FL promotes the survival of primitive hemopoietic progenitor cells, in particular those with an inherent B lymphoid potential.
CD95-dependent bystander lysis caused by CD4+ T helper 1 effectors.
Authors: Wang R , Rogers A M , Ratliff T L , Russell J H 
Published: December 2022

Abstract
CD95-dependent lysis of target cells by CD4+ cells raises important questions of specificity and its potential role in inflammation. Much of what we know about CD95L-dependent killing is in fact bystander killing because the T cells have been previously activated by pharmacologic reagents. In an effort to better understand its significance in a more physiologic setting, we have examined bystander lysis by Th1 cells stimulated by Ag and APC in a murine model system. We find that bystander lysis is readily stimulated by M phi APC but not some epithelial lines, even though they themselves are killed in a CD95-dependent process while serving as APC. Bystander activity requires close proximity between the T cell, the APC, and the bystander target because bystanders are not lysed during coculture in Transwells.
Differential binding avidities of human IgM for staphylococcal protein A derive from specific germ-line VH3 gene usage.
Authors: Hakoda M , Kamatani N , Hayashimoto-Kurumada S , Silverman G J , Yamanaka H , Terai C , Kashiwazaki S 
Published: December 2022

Abstract
Human IgM that express the variable region genes of the VH3 family bind staphylococcal protein A (SPA). We previously reported that the SPA-binding IgM can be divided into two groups based on the differential binding avidities for solid-phase SPA. To study the molecular basis for these differences, we cloned B cells from human blood by EBV transformation. The nucleotide sequences of the expressed Ig heavy chain genes were determined on 20 B cell clones that produce SPA-binding IgM. The germ-line VH3 gene usage in IgM with high avidities for SPA were distinct from the germ-line VH3 genes used in IgM with low avidities for SPA. There was no correlation in the usage of D or JH genes or in the usage of light chains in IgM according to the SPA binding avidity. These results suggest that the differential binding avidities for SPA are at least partly due to specific germ-line VH3 gene usage. An investigation of direct binding of SPA to the synthetic peptides corresponding to the portions of the variable regions of SPA-binding and non-SPA-binding IgM showed that the peptides corresponding to the VH3 family specific framework region 3 sequences had significant SPA binding capacities, while the peptides corresponding to the other subdomains and those corresponding to framework region 3 of the reported VH3 sequences from non-SPA-binding IgM showed little or no binding. It is of interest that the Ig-framework region 3 subdomain corresponds to the fourth hypervariable region, which in the TCR-beta chain has been implicated as a critical site for T cell superantigen binding.
IL-12 gene therapy protects mice in lethal Klebsiella pneumonia.
Authors: Greenberger M J , Kunkel S L , Strieter R M , Lukacs N W , Bramson J , Gauldie J , Graham F L , Hitt M , Danforth J M , Standiford T J 
Published: December 2022

Abstract
IL-12 is a proinflammatory cytokine that has recently been shown to have beneficial effects in the setting of acquired host immunity. To determine the role of IL-12 in innate immunity against Gram-negative bacterial organisms, CBA/J mice were challenged with 10(2) CFU of Klebsiella pneumoniae intratracheally (i.t.), resulting in the time-dependent expression of IL-12 mRNA (p35 and p40) and protein within the lung. Passive immunization of animals with anti-IL-12 serum i.p. at the time of K. pneumoniae inoculation resulted in a 12-fold increase in K. pneumoniae CFU in lung homogenates at 48 h, as compared with animals receiving control serum. In addition, treatment of Klebsiella-infected mice with anti-IL-12 Abs significantly decreased both short and long term survival. To assess the effect of compartmentalized IL-12 overexpression on outcome in Klebsiella pneumonia, animals were treated i.t. with 5 x 10(8) PFU of a nonreplicating adenoviral vector containing a human cytomegalovirus promoter and cDNAs coding for the p35 and p40 subunits of IL-12 inserted into the E1 and E3 domains (Ad5mIL-12), respectively. In vivo transfection with Ad5mIL-12 resulted in 45% long term survival in Klebsiella pneumonia, whereas no animals with Klebsiella pneumonia receiving control adenovirus survived. Moreover, treatment with anti-IFN-gamma Abs or soluble TNF receptor:Ig construct partially and completely attenuated survival benefits observed in animals receiving Ad5mIL-12, respectively. In conclusion, endogenous IL-12 is a critical component of antibacterial host defense, and the compartmentalized overexpression of IL-12 using recombinant adenoviral gene therapy represents a safe and effective approach to deliver IL-12 to the lung in the setting of murine Klebsiella pneumonia.
Protection against lethal influenza virus encephalitis by intranasally primed CD8+ memory T cells.
Authors: Stevenson P G , Hawke S , Bangham C R 
Published: December 2022

Abstract
The neurotropic influenza virus strain A/WSN (H1N1) caused a rapidly fatal encephalitis after intracerebral inoculation into naive mice. Intranasal immunization with the same virus (homotypic) completely protected mice against a subsequent intracerebral challenge with A/WSN; there was no clinical disease, and infectious virus could not be recovered from the brain. In vivo depletion of CD4+ or CD8+ T cell subsets did not affect homotypic protection, and the pups of immune mothers were also protected against a lethal intracerebral challenge with A/WSN, suggesting that the Ab produced by intranasal priming was sufficient to protect mice against later intracerebral infection. Intranasal immunization with the heterotypic influenza strain A/X31 (H3N2) did not generate protective Ab, but despite an acute illness, 80% of mice survived the subsequent intracerebral challenge. Immune protection was associated with CD8+ T cell infiltration throughout the brain substance, together with widespread up-regulation of intracerebral MHC class I and MHC class II expression. In vivo T cell subset depletion showed that heterotypic protection was dependent upon CD8+, but not CD4+, T cells. This model system demonstrates some of the mechanisms through which the immunity generated by an initial extracerebral virus infection may protect against later intracerebral virus replication.
Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways.
Authors: Cory G O , MacCarthy-Morrogh L , Banin S , Gout I , Brickell P M , Levinsky R J , Kinnon C , Lovering R C 
Published: December 2022

Abstract
Wiskott-Aldrich syndrome is an X-linked combined immunodeficiency affecting cells of several different hemopoietic lineages. The Wiskott-Aldrich syndrome protein (WASP), which has no homology with any other known protein families, is rich in proline motifs known to contribute to Src homology 3 binding sites. However, its function has not been determined. The Tec family of cytoplasmic tyrosine kinases, which include Btk (the X-linked agammaglobulinemia gene), Itk, and Tec, is thought to be involved in lymphoid cell signaling pathways. In this work, we show binding of WASP to the Src homology 3 domains of Btk, Itk, Tec, Grb2, and phospholipase C-gamma, which suggests a function for WASP in lymphoid cell signaling.
Beta1 integrin-mediated activation of focal adhesion kinase and its association with Fyn and Zap-70 in human NK cells.
Authors: Rabinowich H , Manciulea M , Herberman R B , Whiteside T L 
Published: December 2022

Abstract
Adhesive interactions mediated by cell surface receptors have been shown to induce signal transduction pathways that regulate changes in cellular function. We have reported recently that fibronectin (FN) receptors, alpha4beta1 and alpha5beta1 integrins, on NK cells transduce transmembrane signals leading to tyrosine phosphorylation of 60-, 70-, and 120-kDa proteins. In the current study, we have identified a 120-kDa phosphoprotein as the focal adhesion kinase (p125FAK), a structurally unique nonreceptor protein tyrosine kinase that localizes to focal adhesions. Activity of p125FAK was induced by adhesion of NK cells to plastic-immobilized FN, by cross-linking of cell surface-bound FN or FN fragments, FN120 or FN40, with anti-FN mAb, or by cross-linking of alpha4beta1 or alpha5beta1 integrins with alpha-chain-specific Abs. We also observed that enhanced in vitro kinase activity was associated with immunoprecipitates of alpha4beta1 or alpha5beta1 integrins from lysates of FN-adherent NK cells as compared with BSA-treated NK cells. In addition to p125FAK activity, FN-induced kinase activity was also found to be mediated by Fyn, Lyn, and Zap-70, as assessed by in vitro phosphorylation of the immunoprecipitated kinases in the presence of [gamma-32P]ATP. Clustering of FN receptors on NK cells by agonists such as immobilized FN or alpha4- or alpha5-specific Abs also induced association of Fyn and Zap-70 with p125FAK. Our observations indicate that activation and phosphorylation of p125FAK as well as Zap-70 and certain kinases of the src family play an important role in formation of active signaling complexes in response to triggering via beta1 integrins on NK cells. These results also suggest the existence of cross-talk or points of convergence between the beta1 integrin-mediated and other receptor-signaling pathways.
NK 1+ CD4- CD8- alphabeta T cells in the peritoneal cavity: specific T cell receptor-mediated cytotoxicity and selective IFN-gamma production against B cell leukemia and myeloma cells.
Authors: Sugie T , Kubota H , Sato M , Nakamura E , Imamura M , Minato N 
Published: December 2022

Abstract
NK1+ double negative (DN) alphabeta T cells were present in the peritoneal exudate cells (PEC) of both normal and athymic B6 mice, accounting for as much as 25% of the total T cells, while their numbers were far less in the PEC of BALB/c and (BALB/c x B6)F1 mice. IL-2-dependent clones established from the DN alphabeta T cell population in the PEC of IL-2 receptor alpha-chain transgenic B6 mice exhibited potent cytotoxicity against a series of B cell lineage leukemias and myelomas, such as CD5+BCL1 and MOPC, without affecting NK-susceptible targets. The cytotoxicity of the clones against BCL1 and MOPC was specifically inhibited by anti-CD3, anti-alphabetaTCR, or anti-relevant Vbeta (Vbeta8) Ab, but not by control Abs, indicating that it was mediated by the specific alphabetaTCR/CD3. Other BALB/c-derived target cells expressing both MHC class I and class II were not affected, and neither Ab against them affected the cytotoxicity, strongly suggesting that the cytotoxicity of NK1+ DN alphabeta T cell clones was independent of the particular MHC Ags. The clones produced IFN-gamma, but little IL-2 or IL-4, in response to anti-CD3 stimulation, to the susceptible, but not resistant, targets, and to IL-12. The clones exhibited TCRalpha (Valpha8) distinct from an invariant TCRalpha (Valpha14) reported to dominate in thymic NK1+ alphabeta T cells. The presence of DN alphabeta T cells with similar functional features in the normal PEC was confirmed by the short term stimulation in vitro. The present results along with other recent reports strongly suggested that, like the mainstream alphabeta T cells, the NK1+ DN alphabeta T cell population consisted of functionally heterogeneous subsets.
Immunoglobulin D(H) recombination signal sequence targeting: effect of D(H) coding and flanking regions and recombination partner.
Authors: VanDyk L F , Wise T W , Moore B B , Meek K 
Published: December 2022

Abstract
V(D)J recombination is targeted by recombination signal sequences (RSS) located immediately adjacent to immune receptor gene segments. While the RSS flanking D(H) segments appear to be equivalent, they are not randomly utilized. During D(H) to J(H) rearrangement, the 3' D(H) RSS is virtually exclusively utilized, suggesting that the 3' D(H) RSS could simply be a better target for the recombinase. However, when we examined V(H) to D(H) (without J(H)) rearrangements, we found that the preference for D(H) RSS use changes, so that the 5' D(H) RSS are preferred. This suggests that the 3' D(H) RSS are not simply superior targets for the V(D)J recombinase, but instead that certain 12/23-bp spacer RSS combinations work better together to target recombination than do others. We have analyzed a series of artificial recombination substrates to delineate cis sequences that affect D(H) RSS selection. Our data suggest that coding sequences adjacent to the D(H) RSS, flanking sequences outside the D(H) gene segment itself, and recombination partner all affect D(H) RSS targeting.
Intestinal transport and catabolism of IgE: a major blood-independent pathway of IgE dissemination during a Trichinella spiralis infection of rats.
Authors: Negrão-Corrêa D , Adams L S , Bell R G 
Published: December 2022

Abstract
Previous work has shown that Trichinella spiralis-infected rats transport IgE from plasma to intestinal tissue and fluids. In this study we quantitate IgE transport to the gut and circulation during T. spiralis infection in rats. Total IgE levels in intestinal fluid from infected rats were elevated by 4 days post-infection (dpi), but were not elevated in serum and lymph until 7 dpi. IgE levels in intestinal fluid ranged from 1 to 6 microg between 10 and 21 dpi, and serum and lymph IgE levels ranged from 100 to 200 ng/ml. Immunoprecipitation of intestinal fluid and enterocyte lysate at 11 dpi showed a protein of 190 kDa that was recognized by mouse anti-rat IgE-MARE-1 in Western blots. This protein was removed from intestinal wash samples with anti-IgE (A2)-Sepharose. The half-life of intact IgE in the intestinal lumen of rats 10 days after infection was 3.25 min. In serum, the half-life of IgE was 5 h. Analysis of IgE production and consumption in 10-day T. spiralis infected rats showed that about 4.67 microg IgE/day entered the serum, while 2570.00 microg IgE/day entered the intestinal lumen. The IgE present in serum 10 days after T. spiralis infection originated in the gut and/or associated lymphoid tissue and was transported to the circulation via thoracic duct lymph. However, most IgE produced in the intestine was transported to the gut lumen at a rate that exceeded transport to plasma by a factor of several-hundredfold.
Regulation by IL-5 of expression of functional platelet-activating factor receptors on human eosinophils.
Authors: Kishimoto S , Shimadzu W , Izumi T , Shimizu T , Fukuda T , Makino S , Sugiura T , Waku K 
Published: December 2022

Abstract
Platelet-activating factor (PAF) and IL-5 are both important mediators of various allergic reactions, although the relationship between these mediators in allergic responses has not yet been fully elucidated. In this study, we investigated the effects of human rIL-5 on the expression of the PAF receptor (PAF-R) on eosinophils from healthy human volunteers. The specific binding of [3H]WEB 2086, a specific ligand for PAF-R, to eosinophils treated with 5 ng/ml of IL-5 for 12 h was significantly higher than that to untreated cells. The Bmax value for IL-5-treated eosinophils was 1.8-fold higher than that for untreated cells, while the Kd values remained unchanged. This clearly indicates that surface expression of PAF-R on eosinophils is enhanced by IL-5. The enhancement was first observed at 6 h and reached a plateau at 12 to 18 h. The effect of IL-5 was abolished in the presence of cycloheximide or actinomycin D. When the relative amount of PAF-R mRNA was determined by reverse transcription PCR, the message was found to be increased through activation of transcription of transcript 1 on exposure to IL-5. Furthermore, we found that the PAF-induced increase in intracellular calcium ion concentration in eosinophils was markedly augmented by exposure to IL-5 for 12 h. Several lines of data suggest that the enhanced expression of PAF-R on eosinophils due to IL-5 is the cause of the augmented response to PAF. These findings will be of value for understanding the mechanisms of selective infiltration and activation of eosinophils in allergic diseases in which PAF and IL-5 are crucially involved.
Enhanced HIV-1 activity in bone marrow can lead to myelopoietic suppression partially contributed by gag p24.
Authors: Rameshwar P , Denny T N , Gascón P 
Published: December 2022

Abstract
Similar to other lymphoid organs, the bone marrow (BM) is a potential reservoir for HIV-1. Although hematologic abnormalities are common in AIDS patients, the mechanisms by which HIV-1 contributes to these abnormalities are poorly understood. Hemapoietic suppression can be mediated by HIV-1 and some of its associated proteins. We have previously reported that AIDS peripheral blood sera inhibit normal CFU-granulocyte macrophage (GM). In this study, we have found that sera obtained from AIDS BM patients are more inhibitory to CFU-GM than those from peripheral blood (p &lt; 0.05). To determine a candidate suppressor factor, we studied the role of p24 and found that it exerts varying degrees of suppression to CFU-GM, but minimal inhibition on erythroid colonies. We have found that the suppressive levels of p24 in in vitro assays are similar to the average circulating levels in AIDS patients. We have also observed that most of the inhibition caused by p24 is mediated by soluble factor(s) produced by the BM stroma. Cross-linking studies with membrane proteins from normal BM stroma and CD34+ cells indicated a putative 26-kDa p24 receptor, indicating that p24 binds to a receptor present on normal BM cells. These results implicate another HIV-1 protein, p24, in hemapoietic suppression and add another plausible mechanism by which HIV-1 contributes to BM failure in AIDS. Furthermore, these findings suggest a potential risk for similar in vivo suppression in the early phase of HIV-1 infection when viremia is elevated, and also in long-term survivors who have low, although persistent, HIV-1 replication.