bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the MHC: isolation of class II beta-chain cDNA clones from the amphibian Xenopus laevis.
Authors: Sato K , Flajnik M F , Du Pasquier L , Katagiri M , Kasahara M 
Published: December 2022

Abstract
The amphibian Xenopus laevis is the most primitive vertebrate in which the MHC has been identified both at the biochemical and functional levels. In the present study, cDNA clones for MHC class II beta-chain genes of X. laevis were isolated using the polymerase chain reaction. In partially inbred animals with the MHC f haplotype, two distinct cDNA clones assumed to encode isotypes were identified. The deduced MHC class II beta-chains of X. laevis had structures fundamentally similar to those of their mammalian counterparts. The overall amino acid sequence identity between X. laevis and representative mammalian MHC class II beta-chains was approximately 41 to 50%. Sequence comparison of cDNA clones isolated from outbred subjects and the partially inbred frog with the MHC f haplotype showed that nucleotide substitutions are located primarily in the beta 1 domain and that non-synonymous substitutions occur more frequently than synonymous substitutions in the putative Ag-binding sites. This result indicates that, as in mammalian MHC genes, the MHC class II beta-chain genes of X. laevis are under positive Darwinian selection. Despite the fact that X. laevis is a tetraploid species, its MHC, as defined by serology, immunochemistry, and MLR, is diploidized. Family studies showed that all MHC class II beta-chain genes detectable in the genome of X. laevis segregate with serologically defined MHC haplotypes, suggesting that the second, inactivated set of MHC class II beta-chain genes was either deleted or that their sequences diverged too far to be detected by DNA hybridization. Furthermore, a nearly constant number of MHC class II beta-chain genes was detectable in most, if not all, Xenopus species with various degrees of ploidy. Thus, various polyploid species of Xenopus appear to have used a similar strategy to diploidize their MHC genes.
Integrin regulation of leukocyte inflammatory functions. CD11b/CD18 enhancement of the tumor necrosis factor-alpha responses of monocytes.
Authors: Fan S T , Edgington T S 
Published: December 2022

Abstract
Engagement of the integrin CD11b/CD18 (alpha M beta 2, Mac-1, CR3) on cells of monocyte (Mo) lineage has recently been demonstrated to enhance synthesis and surface expression of the integral plasmalemma receptor tissue factor. The role of cognate interactions between integrin and its ligands in the regulation of cellular responses important to inflammation can be extended to the effect on the enhancement of TNF-alpha mRNA accumulation and protein secretion by Mo once stimulated by an initial signal such as LPS. At a concentration optimal for inducing TNF-alpha responses, LPS was observed to rapidly increase by two- to threefold the surface expression on Mo of CD11b but not CD11a or CD11c. In the absence of initial signal, engagement of CD11/CD18 integrins per se failed to elicit a TNF-alpha response. In the presence of the initial transcriptional agonist LPS, both TNF-alpha mRNA expression and protein secretion were enhanced several-fold by cells adherent to a CD11b/CD18 ligand, to endothelial cells as well as engagement of CD11b/CD18 integrin by specific antibodies. This enhancement appears to be CD11b/CD18 specific and not from mere attachment or spreading. The enhancement effect after HUVEC binding was inhibited 75% by anti-CD11b mAb M1/70. These studies lead to the hypothesis that engagement of the CD11b/CD18 integrin results in the transduction of cellular signals that quantitatively enhance the expression of inflammatory mediators of Mo-mediated responses.
The serine protease cofactor factor V is synthesized by lymphocytes.
Authors: Shen N L , Fan S T , Pyati J , Graff R , LaPolla R J , Edgington T S 
Published: December 2022

Abstract
Ag-specific cellular immune responses result in CD4+ T cell activation, which can induce the expression of tissue factor in cells of monocyte/macrophage lineage. This results in initiation of the coagulation protease cascade, with ultimate generation of thrombin. The latter is a potent and pleiotropic mediator of cellular responses and deposition of fibrin. To explore the requirements for extravascular cellular mediation of immune effector pathways, we have searched for a cellular source of the cofactor factor Va. Factor V mRNA was identified in human lymphoid cells by using reverse transcription followed by the polymerase chain reaction (RT-PCR). We confirmed our reverse transcription-polymerase chain reaction results by an independent cloning of factor V cDNA from a T cell cDNA library. The sequence of the factor V cDNA was virtually identical to hepatic factor V mRNA sequence. A limited span of mRNA, encoding part of the connecting region of the factor V protein, was found to contain nucleotide polymorphisms based on six nucleotide substitutions. Northern blot analysis confirmed the presence of a approximately 7-kb factor V mRNA in the Hut-78* human T lymphoma cell line and, at five- to eightfold less abundance, in unstimulated lymphocytes and long term allogeneic stimulated T cells. Immunocytology with factor V mAb identified factor V intracellularly in freshly isolated T lymphocytes but not on the surface of cells. These data provide evidence for factor V transcription and biosynthesis by human lymphocytes. They provide an additional perspective on how lymphocytes may contribute to inflammatory effector functions of cellular immune responses in extravascular sites through provision of cofactors necessary for the coagulation serine protease cascade.
Human recombinant macrophage inflammatory protein-1 alpha and -beta and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes.
Authors: Wang J M , Sherry B , Fivash M J , Kelvin D J , Oppenheim J J 
Published: December 2022

Abstract
The human macrophage inflammatory proteins-1 alpha and -beta (MIP-1 alpha and -beta), which are also known as LD78 and ACT2, respectively, are distinct but highly related members of the chemoattractant cytokine (chemokine) family. rMIP-1 alpha and -beta labeled with 125I specifically bind to human peripheral blood monocytes, the monocytic cell line THP-1, peripheral blood T cells, and the YT cell line. Steady state binding experiments revealed approximately 3000 high affinity binding sites/cell for MIP-1 alpha on human monocytes and on THP-1 cells, with Kd values of 383 pM and 450 pM, respectively. Human MIP-1 alpha and -beta had nearly identical affinities for the binding sites and each competed equally well for binding. Human monocyte chemotactic and activating factor (MCAF), a member of the same chemokine family, consistently displaced about 25% of human MIP-1 alpha and -beta binding on monocytes but not on YT cells, which did not bind MCAF. On the other hand, human rMIP-1 alpha and -beta partially inhibited binding of radiolabeled MCAF to monocytes. Both MIP-1 alpha and -beta were chemotactic for human monocytes. Preincubation of monocytes with human rMIP-1 alpha or -beta markedly reduced cell migration towards the other cytokine, whereas preincubation with human rMCAF only partially desensitized the monocyte chemotaxis response to human rMIP-1 alpha or -beta. These data suggest the existence of three subtypes of receptors, i.e., one unique receptor shared by MIP-1 alpha and -beta, a second unique receptor for MCAF, and a third species that recognizes both MCAF and MIP-1 peptides.
Effect of transforming growth factor-beta on early and late activation events in human T cells.
Authors: Ahuja S S , Paliogianni F , Yamada H , Balow J E , Boumpas D T 
Published: December 2022

Abstract
Transforming growth factors-beta (TGF-beta) modulate immune responses by inhibiting the proliferation of normal T lymphocytes. To examine the mechanism(s) of this inhibition, we studied the effect of TGF-beta 1 on selected events associated with the initiation and progression of the T lymphocyte cell cycle. Human peripheral blood T cells were stimulated with anti-CD3 mAb, PHA, PMA, or ionomycin, alone or in combination. TGF-beta 1 (0.5 to 10 ng/ml) partially inhibited the tyrosine phosphorylation of a 100-kDa protein, but not the calcium influx when cells were stimulated via TCR. Nuclear transcription of early activation genes (c-fos, c-jun, and c-myc) as determined by nuclear run-off assays, and steady state mRNA levels and/or protein products of intermediate activation genes (IL-2, IL-2R alpha, IL-2R beta, and transferrin receptor) were not affected by TGF-beta 1. Total cellular RNA synthesis and cell size after T cell stimulation were also not affected by TGF-beta 1. However, TGF-beta 1 inhibited the IL-2-dependent proliferation of Con A lymphoblasts by -50%. This inhibition was associated with the down-regulation of IL-2-mediated tyrosine phosphorylation of proteins of 120, 100, 85, 75, and 50 kDa. TGF-beta 1 also inhibited the IL-2-dependent phosphorylation of the retinoblastoma susceptibility gene product, which plays an important role in cell cycle progression. These results suggest that TGF-beta 1 inhibits T cell proliferation by down-regulating predominantly IL-2-mediated proliferative signals.
A novel T cell activation antigen identified by monoclonal IMN3.1 antibody and expressed preferentially on human T cells susceptible to apoptotic cell death.
Authors: Uehara T , Miyawaki T , Natsuume-Sakai S , Nibu R , Hasui M , Yachie A , Shimizu S , Taniguchi N 
Published: December 2022

Abstract
When cultured without appropriate growth factors, most of activated (CD45RO+) T cells expanded in acute EBV-induced infectious mononucleosis (IM) easily die via an apoptotic cell death mechanism, indicating one Ag-driven selection in the periphery. In this work, we attempted to raise the mAb against cell surface molecules, preferentially expressed on T cells entering apoptosis, by immunizing PBMC from an acute IM patient. We obtained one mAb, termed IMN3.1, that could define clearly the expansion of activated (CD45RO+) T cells in the blood of acute IM patients. In contrast to its intense expression on IM T cells, the IMN3.1-reactive Ag was only dimly expressed on CD45RO+ (memory or previously activated) populations of T cells from normal individuals. Although naive (CD45RO-) populations of T cells usually lacked IMN3.1 Ag, this Ag was inducible relatively late after in vitro activation of naive T cells. The cellular distribution and molecular characterization of IMN3.1-reactive Ag suggested that IMN3.1 mAb appeared to recognize a novel activation-associated cell surface determinant of about 120 kDa m.w., which might be predominantly expressed on apoptosis-prone T cell lineage cells, such as IM T cells, thymocytes, cytokine-dependent T cell lines, and anti-Fas-sensitive T cell lines.
A protein of the AP-1 family is a component of nuclear factor of activated T cells.
Authors: Castigli E , Chatila T A , Geha R S 
Published: December 2022

Abstract
Nuclear factor of activated T cells (NF-AT) is a transcriptional activator involved in the induction of IL-2 gene expression. The response element for NF-AT is a sequence localized between -285/-254 in the IL-2 regulatory region. The composition of NF-AT protein is still not fully elucidated. We demonstrate that, in normal human T cells, an AP-1 protein is a component of the NF-AT protein complex. This was evidenced by the ability of the AP-1 site to compete with the NF-AT site for binding to NF-AT and by the capacity of immobilized anti-Jun and anti-Fos antibodies to deplete NF-AT-binding activity from nuclear extracts of activated T cells. There was no detectable binding of in vitro translated Jun/Fos heterodimer (AP-1) to the NF-AT sequence, and the NF-AT sequence was unable to inhibit the binding of Jun/Fos to the AP-1 sequence. The presence of an AP-1 protein in the NF-AT protein complex may regulate NF-AT-binding activity through protein-protein interaction.
Endogenous Ig production in mu transgenic mice. I. Allelic exclusion at the level of expression.
Authors: Imanishi-Kari T , Bandyopadhay S , Busto P , Huang C A 
Published: December 2022

Abstract
Our findings indicate that allelic exclusion is maintained in B cells that successfully rearrange and express and endogenous H chain gene, despite carrying a functionally rearranged H chain transgene (17.2.25 mu a). Cloned hybridomas having a functionally rearranged endogenous H chain gene as well as the transgene produce only endogenous gene products. Some of these hybridoma cultures, upon continuous growth, will secrete transgene as well as endogenous gene products. However, the two H chain polypeptides appear to be made by different cells. In each of three cases of such "double producer" lines examined, further subcloning at this time reveals two types of clones: those that secrete only transgene and those that secrete only endogenous H chains. The clones producing transgene product have lost the functionally rearranged endogenous H chain genes, whereas the clones producing endogenous gene products still contain both transgene and endogenous functionally rearranged H chain genes. These results indicate that hybridomas expressing endogenous Ig have transgene copies that are potentially functional but are reversibly silenced by an unknown mechanism and suggest that inhibition of transgene expression may be mediated by endogenous Ig gene expression.
Different appearance of gamma delta T cells during salmonellosis between Ityr and Itys mice.
Authors: Emoto M , Naito T , Nakamura R , Yoshikai Y 
Published: December 2022

Abstract
Ity gene, which is believed to be a single gene on proximal mouse chromosome 1, determines susceptibility to Salmonella infection. We have recently demonstrated that the gamma delta T cells specific for purified protein derivative appear at the early stage after infection with Salmonella choleraesuis strain 31N-1 (avirulent strain) in mice. In the present study, we compared the appearance of the gamma delta T cells in Ityr and Itys mice after infection with S. choleraesuis in an attempt to elucidate the role of the gamma delta T cells in the in vivo effect of the Ity locus on murine salmonellosis. The numbers of gamma delta T cells in the peritoneal cavity and liver were significantly larger in DBA/2 (Ityr) mice than those in BALB/c (Itys) mice after infection with a sublethal dose of S. choleraesuis. C.D2 Ityr mice, which are BALB/c mice with Ityr allele, also showed a significant increase in the number of the gamma delta T cells at the early stage after infection. Similar results in different appearances of the gamma delta T cells could be obtained between BALB/c and DBA/2 mice after infection with Mycobacterium bovis, bacillus Calmette-Guérin. The peritoneal adherent cells of DBA/2 mice infected with S. choleraesuis, which expressed a large amount of heat shock/stress protein (hsp) homologous to the mycobacterial 65-kDa hsp, induced significantly higher level of expansion of the peritoneal gamma delta T cells in normal mice in vivo and in vitro than did those of BALB/c mice infected with S. choleraesuis, which expressed a lesser amount of the hsp. These results suggest that the Ity locus may be closely related to the expression of hsp by macrophages after infection with Salmonella, which in turn stimulate the gamma delta T cells in the host during an early phase of salmonellosis.
Macrophage-dependent candidacidal mechanisms in the murine system. Comparison of murine Kupffer cell and peritoneal macrophage candidacidal mechanisms.
Authors: Redmond H P , Shou J , Gallagher H J , Kelly C J , Daly J M 
Published: December 2022

Abstract
Candida albicans infection is common in immunocompromised patients. The role of fixed tissue macrophages (M phi), including Kupffer cells (KC) and peritoneal macrophages (PM phi), in host defense against C. albicans is unclear. This study examined murine M phi candidacidal mechanisms and evaluated the in vitro role of the macrophage-activating factor IFN-gamma in augmenting these mechanisms. The effect of in vivo administration of IFN-gamma on survival after lethal C. albicans challenge in the murine system was also assessed. Percent PM phi and KC ingestion of C. albicans were similar. Prior opsonization of Candida increased the percentage of M phi ingestion of this pathogen. PM phi and KC phagocytic function was similar for both nonopsonized and opsonized C. albicans, but KC demonstrated markedly decreased ability to kill this pathogen (O2-, Candida killing). IFN-gamma enhanced KC and PM phi candidacidal activity. PM phi and KC Ag presentation was increased in early Candida infection, but diminished in established infection, when the majority of animals died. C. albicans failed to elicit significant amounts of either IL-1 or TNF compared with LPS stimulation of PM phi and KC in vitro. IFN-gamma treatment in vivo was associated with significantly improved survival (p &lt; 0.01).
Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression.
Authors: Broxmeyer H E , Sherry B , Cooper S , Lu L , Maze R , Beckmann M P , Cerami A , Ralph P 
Published: December 2022

Abstract
Macrophage inflammatory protein (MIP)-1 alpha, part of a family termed chemokines, has been implicated in suppression of hemopoietic stem and progenitor cell proliferation. The chemokine family has been organized into two subgroups with MIP-1 alpha, MIP-1 beta, macrophage chemotactic and activating factor (MCAF) and RANTES belonging to one subgroup, and GRO-alpha, MIP-2 alpha (GRO-beta), MIP-2 beta (GRO-gamma), platelet factor 4 (PF4), IL-8, and neutrophil activating peptide (NAP)-2 belonging to the other. These molecules were evaluated for effects on colony formation by human bone marrow multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. None of the chemokines stimulated colony formation in the absence of CSF, or influenced colony formation stimulated by a single growth factor such as granulocyte-macrophage-CSF or erythropoietin. However, MIP-1 alpha, MIP-2 alpha, PF4, IL-8, and MCAF suppressed in dose-response fashion colony formation of immature subsets of myeloid progenitor cells stimulated by GM-CSF plus steel factor. Effects were apparent on low density and CD34 HLA-DR(+)-sorted marrow cells in which up to 88.4% of the cells were composed of progenitor cells, suggesting direct effects on the progenitors themselves. Up to 2500-fold less of each chemokine could be used to demonstrate synergistic suppression when any two of these five chemokines were used together at low concentrations, effects also apparently directly on the progenitors. In contrast, MIP-1 beta, MIP-2 beta, GRO-alpha, NAP-2, and RANTES were not suppressive nor did they synergize with MIP-1 alpha, MIP-2 alpha, PF4, IL-8, or MCAF to suppress. However, a fivefold excess of MIP-1 beta blocked the suppressive effects of MIP-1 alpha. Similarly, a fivefold excess of either MIP-2 beta or GRO-alpha blocked the suppressive effects of IL-8 and PF4. These suppressing, synergizing and blocking effects may be of relevance to blood cell regulation.
Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells.
Authors: Cepek K L , Parker C M , Madara J L , Brenner M B 
Published: December 2022

Abstract
Intestinal intraepithelial lymphocytes (iIEL) are a distinct subpopulation of T lymphocytes diffusely distributed in the epithelium. Because &gt; 95% of these iIEL express the integrin alpha E beta 7, we reasoned that this integrin might mediate the localization of iIEL to the epithelium. We report that cultured iIEL bound to mucosal epithelial cells derived from either breast or intestine. This binding was dependent on the presence of divalent cations, and was blocked by mAb specific for two integrins, alpha E beta 7 and alpha L beta 2. After TGF-beta 1 treatment, cultured iIEL cell lines expressed alpha E beta 7 at levels similar to those found on iIEL in vivo. Under these conditions this integrin appeared to predominate in mediating the adhesion of iIEL to epithelial cells. Although alpha L beta 2 blocked the adhesion of iIEL to both endothelial and epithelial cells, alpha E beta 7 blocked binding only to epithelial cells suggesting that the ligand for alpha E beta 7 is not expressed on IL-1 beta-treated cultured endothelial cells. iIEL did not readily bind to the apical surface of confluent polarized epithelial cell monolayers. However, iIEL did bind to these cells when tight junctions were disrupted, a treatment that allows redistribution of proteins compartmentalized to the basolateral surface. This binding was also blocked by mAb to alpha E beta 7. In addition, in vitro coculture of iIEL with polarized epithelial cells resulted in basolateral localization of the iIEL. Thus, it is likely that expression of the alpha E beta 7 ligand is restricted to the basolateral membrane of polarized epithelial cells. Because alpha E beta 7 appears to be a predominant integrin on freshly isolated iIEL, we hypothesized that alpha E beta 7-mediated adhesion may be particularly important in cell-to-cell interactions between T cells and epithelial cells in vivo.
Cytokines and dexamethasone modulation of IL-1 receptors on human neutrophils in vitro.
Authors: Shieh J H , Peterson R H , Moore M A 
Published: December 2022

Abstract
Modulation of IL-1R on human neutrophils was investigated after in vitro treatment of cells with human recombinant (hr) granulocyte (G)-CSF, hrgranulocyte-macrophage (GM)-CSF, hrCSF-1, hrIL-1 alpha, hrIL-2, hrIL-3, hrIL-4, hrIL-5, hrIL-6, hrIL-7, transforming growth factor-beta 1, or hrTNF-alpha. At 4 degrees C, 125I-IL-1 binding was competed by IL-1 but not by other cytokines tested. At 37 degrees C, GM-CSF, TNF-alpha, and IL-1 decreased 125I-IL-1 binding in a dose-dependent manner. Kinetic studies showed that GM-CSF reduced &gt; 45% IL-1 binding within 15 min but later (8 h) produced a &gt; 2-fold increase. In contrast, TNF decreased &gt; 85% IL-1 binding within 15 min with a recovery of &gt; 80% relative to that of control after 24 h. Scatchard analysis revealed that TNF or GM-CSF down-modulation of IL-1 binding was due to a decrease of IL-1R number. Further studies showed that dexamethasone and GM-CSF (or G-CSF) synergistically increased IL-1 binding after 8 h. This synergistic modulation was a cytokine dose- and time-dependent process, and was due to an increase in IL-1R numbers rather than a change in binding affinity. In addition, human bone marrow neutrophils, cord blood neutrophils, and several human hematopoietic cell lines (HL-60, U-937, and AML-193) responded to dexamethasone and GM-CSF (or G-CSF) with a superadditive increase in IL-1 binding. Because mammalian systems respond to bacterial endotoxins with secretion of TNF, IL-1, glucocorticoids, G-CSF and GM-CSF, our results shed additional light on this highly regulated cytokine network and revealed a novel role for GM-CSF.