bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycosyl phosphatidylinositol membrane anchor is not required for T cell activation through CD73.
Authors: Resta R , Hooker S W , Laurent A B , Shuck J K , Misumi Y , Ikehara Y , Koretzky G A , Thompson L F 
Published: December 2022

Abstract
Ecto-5'-nucleotidase (5'-NT,) CD73 is a glycosyl phosphatidylinositol (GPI)-anchored differentiation Ag and purine salvage enzyme expressed on the surface of subsets of human lymphocytes. CD73 mAbs, in combination with submitogenic PMA or OKT3, activate human T cells to proliferate, secrete IL-2, and express IL-2 receptors. For several GPI-anchored proteins implicated in T cell activation, activation is thought to occur through a mechanism that requires the GPI anchor. To investigate the role of the GPI anchor in CD73-mediated signal transduction, CD73 cDNA was transfected into the human T cell leukemia line Jurkat. Transfectants were stimulated to secrete IL-2 by immobilized OKT3 + PMA and by soluble CD73 mAb + PMA. The amount of IL-2 synthesized by individual clones in response to CD73 mAb + PMA was proportional to the IL-2 response to immobilized OKT3 + PMA. CD73 transfectants of Jurkat mutants defective in the TCR, in p56lck, or in the tyrosine phosphatase CD45 did not secrete IL-2 in response to CD73 mAb + PMA, suggesting a role for the CD3/TCR-signaling complex in CD73-mediated signal transduction. A transmembrane form of CD73 was expressed in Jurkat cells by fusing the extracellular portion of CD73 to the transmembrane domain of human tissue factor. Although as a group, clones expressing transmembrane CD73 synthesized less IL-2 in response to CD73 mAb + PMA than clones expressing the GPI-anchored form of the molecule, the responses of the two groups overlapped considerably. In contrast to previous studies with Ly-6, Qa-2, and CD55, the GPI anchor is not critical for activation through CD73.
Ly-49 multigene family expressed by IL-2-activated NK cells.
Authors: Smith H R , Karlhofer F M , Yokoyama W M 
Published: December 2022

Abstract
The susceptibility of a target cell to killing by NK cells is inversely correlated with target cell expression of MHC class I molecules. We have recently demonstrated that a murine NK cell surface molecule, Ly-49, is a primary determinant of IL-2-activated NK cell specificity by apparently acting as an inhibitory receptor. Ly-49 seems to interact with polymorphic regions of certain MHC class I molecules on target cells, yet is expressed only by a subset (15 to 20%) of NK cells. If the interaction between Ly-49 and MHC class I represents a paradigm for understanding IL-2-activated NK cell specificity and putative inhibitory IL-2-activated NK cell receptors, these effector cells should express other molecules, perhaps related to Ly-49, that provide the inhibitory receptor function. We now report the isolation of cDNAs, encoding polypeptides related to Ly-49, from a CD3-, IL-2-activated NK cell library. Full length PCR products were also cloned and sequenced, confirming expression in IL-2-activated NK cells. These cDNAs were homologous to the Ly-49 cDNA and seem to be derived from distinct genes. The new cDNAs encode type II integral membrane proteins having lectin superfamily homology and 66 to 79% amino acid identity with Ly-49A. In contrast to previous reports, these cDNAs cannot be allelic variants because they were all isolated from C57BL/6-derived cells. On the basis of nucleotide homology, the cDNAs could be segregated into five groups; one with Ly-49 itself (now termed Ly-49A) and four others containing distinct sequences. One of the new groups comprised three cDNAs that shared identical sequences, but differed from one another by deletions or insertions of short DNA segments in the predicted extracellular region of the polypeptides. Thus, IL-2-activated NK cells express mRNAs for multiple, Ly-49-related molecules.
Light chain isotype regulation in the horse. Characterization of Ig kappa genes.
Authors: Ford J E , Home W A , Gibson D M 
Published: December 2022

Abstract
Horse Ig kappa genes have been characterized to determine whether there may be a structural basis for the low level of kappa expression in this species. The overall organization of the J kappa-C kappa locus is remarkably similar to that of the mouse and human loci. A single C kappa exon is separated by 2.9 kb from five J kappa segments, four of which seem functional and three of which are associated with canonical recombination signal sequences. A highly conserved intron enhancer was identified upstream of the C kappa exon and a single restriction fragment in horse genomic DNA hybridized strongly with the mouse downstream kappa enhancer. Germ-line and splenic cDNA V kappa sequences were characterized and found to encode N-terminal amino acid sequences previously found by protein sequencing. Hybridization of horse genomic DNA with the horse V kappa-1 germ-line gene and a variety of mouse V kappa-region probes provided evidence for at least 20 V kappa gene segments. The results indicate that the horse possesses a functional kappa locus with a complement of variable region gene segments potentially as large as that previously found at the lambda locus although the exact numbers of functional variable region genes remains to be established for both loci. This finding suggests that the predominance of lambda-chains in horse Ig may not be simply a result of a lack of functional kappa genes or of a disproportionate number of lambda vs kappa variable region genes. The results are discussed in terms of various models of isotype regulation.
Bovine parainfluenza-3 virus selectively depletes a calcium-independent, phospholipid-dependent protein kinase C and inhibits superoxide anion generation in bovine alveolar macrophages.
Authors: Dyer R M , Majumdar S , Douglas S D , Korchak H M 
Published: December 2022

Abstract
Bovine parainfluenza-3 (PI-3) virus inhibits oxygen-dependent bacterial killing by phagocytes, a key pulmonary defense, thus predisposing the host to intrapulmonary bacterial superinfection. PI-3 virus inhibited opsonized zymosan or PMA-activated superoxide anion (O2-) generation in bovine alveolar macrophages. The respiratory virus influenza also inhibits O2- generation by phagocytes, however, the mechanisms(s) of viral inhibition differs from PI-3. PI-3 did not trigger O2- generation before inhibition, whereas influenza triggered O2- generation before desensitization of ligand-initiated respiratory burst. PI-3 modified the twin signals of calcium and protein kinase C in alveolar macrophages. PI-3 infection increased macrophage membrane permeability to extracellular calcium, but did not inhibit calcium mobilization triggered by opsonized zymosan. These effects further distinguish bovine PI-3 from human influenza, which triggers mobilization of cell-associated calcium and inhibits calcium mobilization activated by physiologic ligands. Macrophages possessed two classes of PKC activity, a calcium/phosphatidylserine/diglyceride (Ca/PS/DG))-dependent activity and a Ca-independent, PS/DG-dependent histone IIIS phosphorylating activity. PI-3 infection selectively depleted the Ca-independent, PS/DG-dependent kinase activity but not the classical Ca/PS/DG-dependent activity. Inhibition of Ca-independent, PS/DG-dependent kinase activity and inhibition of O2- generation by PI-3 occurred at a similar viral dose and time frame, suggesting a role for this kinase in activating the respiratory burst. Inhibition of the oxygen-dependent bactericidal function of alveolar macrophages and disturbances in signal transduction may contribute to the immunosuppression and bacterial superinfection accompanying viral respiratory disease.
T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA.
Authors: Elliott D E , Metwali A , Blum A M , Sandor M , Lynch R , Weinstock J V 
Published: December 2022

Abstract
Schistosomiasis mansoni is a disease characterized by liver and intestinal granulomas. Previous investigations in our laboratory showed that nylon wool-adherent CD4+ T lymphocytes isolated from murine hepatic schistosome granulomas express receptors for somatostatin 1-14. Moreover, somatostatin 1-14 substantially decreased IFN-gamma and IgG2a, but not IL-5 secretion by dispersed granuloma cells. This paper extends these observations by defining the somatostatin receptor (SSTR) isoform most likely expressed by granuloma inflammatory lymphocytes. Amplification of mRNA by reverse transcription PCR shows SSTR1, SSTR2, and SSTR3 mRNA in normal mouse brain and other tissues. Nevertheless, only the SSTR2 PCR product was amplified from granuloma cell RNA. The nucleotide sequence of the granuloma SSTR2 PCR product from inflammatory cells is identical to the CBA murine brain SSTR2 cDNA sequence. Granuloma-derived T cell lines, FACS-isolated granuloma CD4+ T cells, thymocytes, splenocytes, and cloned T cell lines all contain mRNA for SSTR2 by reverse transcription PCR. Moreover, both SSTR2A and the splice variant SSTR2B can be amplified from dispersed granuloma cells, granuloma T cell lines, thymocytes, and splenocytes. This is the first demonstration that inflammatory cells produce mRNA for an authentic somatostatin receptor. It is probable that the lymphocyte SSTR2 receptor mediates somatostatin-induced modulation of IFN-gamma secretion.
Loss of HLA haplotype and B locus down-regulation in melanoma cell lines.
Authors: Marincola F M , Shamamian P , Alexander R B , Gnarra J R , Turetskaya R L , Nedospasov S A , Simonis T B , Taubenberger J K , Yannelli J , Mixon A 
Published: December 2022

Abstract
The expression of HLA class I molecules on tumor cells is vital for CD8+T cell recognition of tumor Ags. Loss of HLA class I Ag expression as a result of defective beta 2-microglobulin genes has been described in melanoma cells. To further evaluate mechanisms of tumor escape, HLA class I Ag expression was compared in 24 metastatic melanoma cell lines and 20 melanocyte strains by FACS analysis with use of allele-specific mAbs. Total loss of HLA class I Ag expression was not noted; instead, two relatively common phenomena were identified: 1) A variable degree of expression of HLA-B Ags by melanoma cell lines and melanocytes; however, HLA-A Ags were consistently expressed in all cell types. Furthermore, HLA-B locus Ag expression was detected in vivo in only one of six frozen section specimens obtained from six patients having metastatic melanoma. 2) Loss of allelic expression was noted in two of 14 HLA-A2 (14%) and one of three HLA-A29 (33%) melanoma cell lines and included a full haplotype, which suggests loss of a genomic fragment. Allele-specific PCR amplification demonstrated deletion of genes in linkage disequilibrium within the MHC class II, III, and I regions. Aberrations of HLA class I expression in tumor lines should be considered when assessing MHC-restricted phenomena in in vitro models.
IFN-alpha inhibits antigen-induced eosinophil and CD4+ T cell recruitment into tissue.
Authors: Nakajima H , Nakao A , Watanabe Y , Yoshida S , Iwamoto I 
Published: December 2022

Abstract
In a murine model of airway late phase reaction, we have previously shown that Ag-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and IL-5. To determine whether IFN-alpha regulates Ag-induced eosinophil recruitment into tissue, we studied the effects of rIFN-alpha, endogenous IFN-alpha production induced by poly I.C, and anti-IFN-alpha mAb on the eosinophil infiltration of the trachea induced by Ag inhalation in mice. The i.p. administration of rIFN-alpha prevented Ag-induced eosinophil infiltration in the trachea of sensitized mice. In addition, the inhibitory effect of rIFN-alpha on Ag-induced eosinophil infiltration was not recovered by pretreatment with anti-IFN-gamma mAb. The administration of rIFN-alpha also inhibited Ag-induced CD4+ T cell infiltration in the trachea. However, the administration of rIFN-alpha did not significantly affect blood eosinophil counts nor the number of blood and splenic CD4+ T cells. On the other hand, pretreatment with anti-murine IFN-alpha mAb enhanced Ag-induced eosinophil and CD4+ T cell infiltration in the trachea. Finally, endogenous IFN-alpha/beta production induced by poly I.C also inhibited Ag-induced eosinophil infiltration in the trachea and this inhibition of the eosinophil infiltration was abrogated by pretreatment with anti-IFN-alpha/beta mAb. These results indicate that IFN-alpha suppresses Ag-induced eosinophil and CD4+ T cell recruitment into tissue.
Anti-neutrophil cytoplasmic antibodies engage and activate human neutrophils via Fc gamma RIIa.
Authors: Porges A J , Redecha P B , Kimberly W T , Csernok E , Gross W L , Kimberly R P 
Published: December 2022

Abstract
The presence of anti-neutrophil cytoplasmic Abs (ANCA) in many patients with systemic vasculitis suggests that ANCA may play a role in disease pathogenesis. Neutrophils from patients with Wegener's granulomatosis often express ANCA target Ags (myeloperoxidase (MPO) and proteinase 3 (PR3)) on their surface, making these intracellular primary granule enzymes accessible to these autoantibodies. Similarly, normal neutrophils can be induced to translocate MPO and PR3 to the cell surface in vitro, and we demonstrate that murine mAb ANCA IgG, but not IgM, binds to the ANCA target and engages the Fc gamma RIIa ligand-binding site on the surface of human neutrophils. In contrast to ANCA IgM, ANCA IgG also induces an oxidative burst in neutrophils (oxidation of dihydrorhodamine = 91 +/- 15 fluorescence units with anti-PR3 IgG vs 17 +/- 2 with anti-PR3 IgM, p &lt; 0.001). Blockade of the ligand-binding site of Fc gamma RIIa with an antibinding site mAb Fab significantly reduces this ANCA IgG-triggered production of reactive oxygen species (p &lt; 0.01). Similarly, human ANCA bind the ANCA target, engage Fc gamma RIIa, and induce an oxidative burst in neutrophils. The allelic phenotype of Fc gamma RIIa strongly influences the Fc gamma receptor engagement by ligand, and Fc gamma RIIa homozygous donors differ by more than threefold in the quantitative production of reactive oxygen intermediates (ROI) (p &lt; 0.01). Thus, engagement of Fc gamma RIIa by the Fc region of ANCA is one mechanism by which these autoantibodies activate receptor-mediated signal transduction systems in human neutrophils to initiate programs of inflammation and tissue injury. Fc gamma receptor alleles may represent heritable disease risk factors influencing the magnitude of such a process.
Intrinsic human glomerular mesangial cells can express receptors for IgG complexes (hFc gamma RIII-A) and the associated Fc epsilon RI gamma-chain.
Authors: Radeke H H , Gessner J E , Uciechowski P , Mägert H J , Schmidt R E , Resch K 
Published: December 2022

Abstract
Immune complexes localize to the glomerular mesangium in many forms of human glomerulonephritis. In this investigation, we determined whether primary cultured human glomerular mesangial cells (HMC) express mRNA and functional protein of FcR for IgG. Performing reverse transcription-PCR with subsequent control Southern blots, we showed that in contrast to human monocytes or granulocytes, mRNA for Fc gamma RI and Fc gamma RII is not detectable in either growth-arrested (48 h serum free) or unstimulated proliferating (medium with 10% FCS) HMC. However, IFN-gamma in combination with LPSE.coli (LPS), but not LPS alone elicited a significant transcription of hFc gamma RIII mRNA in resting HMC, whereas cytokines, such as IL-1 beta or TGF-beta, failed to induce any of the three Fc gamma Rs in resting HMC. Proliferating HMC showed a basal transcription of Fc gamma RIII mRNA, which was enhanced by IFN-gamma in combination with LPS. Slot-blot analysis indicated that only the Fc gamma RIII-A gene encoding the transmembrane isoform of Fc gamma RIII was expressed by HMC. For the first time, transcripts for the gamma-chain of Fc epsilon RI were found in HMC. Fc gamma RIII protein expression was detected after LPS/IFN-gamma stimulation both by specific staining of paraformaldehyde-fixed HMC and immunoprecipitation of Fc gamma RIII protein from HMC membranes. Fc gamma RIII-A receptors are functionally active, as HMC IL-6 mRNA synthesis was stimulated by heat-aggregated IgG or F(ab')2 fragments of CLBGran1 mAb only after induction of Fc gamma RIII-A. These in vitro data suggest that HMC that are basically negative for Fc gamma RIII can be stimulated to express low affinity Fc gamma Rs, and thus may participate actively in human glomerulonephritis involving immune complexes.
Inhibition of macrophage Ia expression by nitric oxide.
Authors: Sicher S C , Vazquez M A , Lu C Y 
Published: December 2022

Abstract
Bacterial LPS inhibits the expression of Ia by macrophages stimulated by IFN-gamma. We now present the following observations that suggest a causal relationship between nitric oxide (NO) and this inhibition of Ia expression: 1) NO production precedes inhibition of Ia, 2) the ability of LPS to inhibit Ia expression by IFN-gamma stimulated macrophages is correlated in a dose-dependent fashion with NO production, 3) Ia expression is restored if NO production is inhibited by NG-monomethyl-L-arginine or culturing the macrophages in L-arginine-free medium, and 4) exogenous NO inhibits IFN-gamma-stimulated Ia expression. Taken together these experiments indicate that NO inhibits macrophage expression of Ia. Furthermore, the following studies showed that inhibition of Ia by NO was not due to macrophage death: trypan blue exclusion, macrophage adhesion, conversion of the tetrazolium dye (MTT) to its formazan by a functioning electron transport system, and phagocytosis of IgG opsonized SRBCs. By inhibiting Ia expression, NO may inhibit Ag-presentation to T cells, secretion of IFN-gamma by these T cells, and ultimately inhibit the IFN-gamma-dependent production of NO synthetase. This inhibitory mechanism may prevent excessive NO formation and tissue injury.
Role of CD27 in T cell immune response. Analysis by recombinant soluble CD27.
Authors: Agematsu K , Kobata T , Sugita K , Freeman G J , Beckmann M P , Schlossman S F , Morimoto C 
Published: December 2022

Abstract
CD27 is a disulfide-linked 120-kDa transmembrane glycoprotein expressed on the majority of T cells, B cells, and NK cells; it has homology to a family of molecules that includes the receptors for nerve growth factor and TNF. Previous studies strongly suggest that the CD27 molecule plays a key role in the process of T cell activation. To further determine its role in T cell activation, a recombinant soluble molecule composing only the extracellular domain of CD27 was produced by transfection of Chinese hamster ovary cells. We have defined the binding properties of recombinant soluble CD27 (rsCD27) to CD27 ligand (CD27L) cDNA transfected NIH 3T3 cells and have determined its functional effects on in vitro T cell activation as well as on PWM-driven B cell IgG synthesis. rsCD27 bound specifically to CD27L and the binding was inhibited by one of our anti-CD27 mAbs, anti-1A4, suggesting that the 1A4 epitope of CD27 plays a role in the binding to CD27L. Functionally, rsCD27 inhibited T cell proliferation induced by various stimuli, such as PHA, tetanus toxoid, and anti-CD2, as well as PWM-driven B cell IgG synthesis, similar to the effects of adding anti-1A4. Determination of CD27L expression showed that CD27L mRNA is induced rapidly on activated T and B cells. Taken together, these results provide direct evidence that CD27-CD27L interaction plays a critical role in T cell activation as well as in T cell-dependent B cell IgG synthesis, suggesting that the CD27-CD27L interaction may constitute a component of the T cell-T cell or T cell-B cell interaction seen after activation with Ag or mitogen.
Cellular mechanisms that maintain neonatally-induced tolerance of class II alloantigens. Evidence that factor-mediated suppression silences cytotoxic T cell activity.
Authors: Matriano J A , Socarras S , Streilein J W 
Published: December 2022

Abstract
Virtually all neonatal mice of the A strain background are rendered profoundly and permanently tolerant of test skin allografts if they receive an i.v. inoculation of semiallogeneic hematopoietic cells expressing class II disparate alloantigens. After neonatally injected mice reach immunologic maturity, their lymphoid organs have been found to contain 1) tolerogen-specific CD4+ T cells that proliferate and secrete IL-4 when stimulated in vitro with class II tolerogens and 2) tolerogen-specific CD8+ T cell that fail to differentiate into cytotoxic effector cells. In this study, experiments are described that investigate the possibility that tolerance is maintained by regulatory T cells of the Th2-type. When A.TH T cells were stimulated in vitro with A.TL alloantigens in the presence of lymphoid cells from tolerant mice, tolerogen-specific cytotoxic T cells responses were absent or greatly diminished. When regulatory cells from tolerant mice were fractionated and tested, the cell type responsible for suppression proved to be CD4+ class II tolerogen-specific and gamma irradiation sensitive. Moreover, suppression of tolerogen-specific cytotoxic T cell generation was achieved when regulatory cells and naive responder cells were separated by a transwell barrier and supernatants harvested from cultures in which tolerant cells were stimulated specifically with class II tolerogens also inhibited cytotoxic T cell generation. Thus, suppression appears to be mediated by a soluble factor(s) produced by regulatory T cells. We conclude that tolerance of class II alloantigens is maintained, at least in part, by regulatory cells of the Th2-type that secrete factors that suppress the generation of tolerogen-specific effector cells required for rejection of solid tissue allografts.
Transmission of an Mls-1a-like superantigen to BALB/c mice by foster-nursing on F1 Mls-1bxa mothers. Sex-influenced onset of clonal deletion.
Authors: Piazzon I , Goldman A , Torello S , Nepomnaschy I , Deroche A , Dran G 
Published: December 2022

Abstract
Foster nursing of BALB/c (Mls-1b) mice on (BALB/cxAKR/J)F1 and (BALB/cxDBA/2)F1 (Mls-1bxa), but not on (BALB/cxC57Bl/6)F1 or (BALB/cxC3H/He)F1 (Mls-1bxb mothers, induced the progressive deletion of V beta 6+ and V beta 8.1+ T cells in 50% of the litter. The onset of this Mls-1a-like clonal deletion was markedly sex-influenced, being earlier in females (8-10 wk of age) than in males (32 wk). In both sexes, CD4+ V beta 6+ cells were more affected than CD8+ V beta 6+ cells. Decreases in the percentage of V beta 6+ cells were detected simultaneously in the thymus, lymph nodes, and peripheral blood. Preceding clonal deletion, functional unresponsiveness of CD4+ T cells to Mls-1 a Ags and to anti-V beta 6 Abs could be detected in most young male and female mice. The transmission of the Mls-1a-like superantigen through foster-nursing on (BALB/cxAKR/J)F1 mice correlated with the presence in milk of the mouse mammary tumor virus envelope protein gp52.
Antigen-specific early primary humoral responses modulate immunodominance of B cell epitopes.
Authors: Vijayakrishnan L , Kumar V , Agrewala J N , Mishra G C , Rao K V 
Published: December 2022

Abstract
Accumulation of primary Abs against two distinct epitopes on a designed polypeptide, MEP-1, was examined. The early primary response was predominantly against a C-terminal epitope (MEP 77-100), although subsequent maturation established an epitope within the N-terminal half (MEP 17-31) as the immunodominant one. Inversion of immunodominance correlated with the inability of anti-MEP 77-100 B cells to interact productively with T cells, which consequently received reduced help. Interaction between epitope-specific B and T cells was found to be attenuated in the presence of early primary anti-MEP-1 antiserum, and the extent of inhibition was directly proportional to the level and affinity of epitope-specific Igs. Therefore, it seems that early primary Abs to a multideterminant Ag selectively down-regulate maturation of epitope-specific primary humoral responses.