bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-reactive, T cell receptor-gamma delta+, lymphocytes from the intestinal epithelium of weanling mice.
Authors: Nagler-Anderson C , McNair L A , Cradock A 
Published: December 2022

Abstract
Intraepithelial T lymphocytes (IEL) are dispersed throughout the intestinal epithelial lining but their role in cellular immune defense is unknown. Their location suggests that their highly activated state may be due to constant exposure to bacterial Ag. To study IEL specificity and function we have prepared a panel of IEL-T cell hybridomas from both adult and weanling C57B1/6 mice. Many of these expressed TCR-gamma delta, a cell type rare in peripheral lymph nodes and spleen but predominant at epithelial surfaces. We have identified a subset of gamma delta T cells from weanling mice which is self reactive, i.e., these hybrids secrete IL-2 spontaneously, without antigenic stimulation or a requirement for APC. Self-reactive TCR-gamma delta+ hybrids and lines, all of which bear a particular TCR (V gamma 1.1C gamma 4V delta 6), have previously been derived from neonatal thymus and the skin. Northern blot and immunoprecipitation analyses suggest that the self-reactive IEL hybrids also bear a C gamma 4/V delta 6 TCR. Antibody inhibition experiments showed that the self-reactivity of the IEL hybrids is TCR mediated. Spontaneous IL-2 production was blocked by soluble anti-CD3 and anti-TCR-gamma delta antibodies but not by antibodies to the TCR-alpha beta. The self-reactive IEL hybrids lack class II MHC and the class I-like proteins CD1 and TLA but express class I MHC. IEL hybrids may also require the vitronectin receptor as an accessory molecule for their activation because spontaneous IL-2 production is blocked by antibody to the vitronectin receptor as well as by the extracellular matrix protein active site peptide RGDS, but not the control peptide RGES. V gamma 1.1C gamma 4V delta 6 T cells in the thymus, skin, and intestine may represent a small and unique subpopulation of lymphocytes with a potential for autoimmune reactivity at peripheral sites.
Limited T cell receptor beta-chain usage in the sperm whale myoglobin 110-121/E alpha dA beta d response by H-2d congenic mouse strains.
Authors: Sellins K S , Danska J S , Paragas V , Fathman C G 
Published: December 2022

Abstract
The specificity and TCR gene usage of a panel of sperm whale myoglobin (SpWMb)-reactive T cell clones from DBA/2 mice have previously been characterized, to study structure-function relationships between components of the ternary complex consisting of Ag, TCR, and MHC class II molecules, whose interaction leads to Th cell activation. These DBA/2 clones were specific for epitopes within the residue 110 to 121 region of SpWMb, in the context of the mixed isotype molecule E alpha dA beta d, and expressed the TCR V beta 8.2 gene element. SpWMb-specific T cell hybridomas from the H-2d-congenic B10.D2 mouse strain, which differs from the DBA/2 strain only in the non-MHC background, were generated and compared with the T cell hybridomas from DBA/2 mice, in order to investigate the influence of non-MHC genes on the specificity of the T cell response to the 110-121 epitope. V beta usage by these hybridomas was very homogeneous; three of three DBA/2 and eight of nine B10.D2 hybridomas specific for the 110-121 epitope, in the context of the mixed isotype molecule E alpha dA beta d, expressed the V beta 8.2 gene product. Nucleotide and amino acid sequences of D beta, J beta, and N regions were also similar. One 110-121/E alpha dA beta d-specific B10.D2 hybridoma used V beta 7, a V beta that is clonally deleted in DBA/2 mice. These experiments suggest that a similar set of TCR beta genes are used to respond to a given epitope, regardless of non-MHC background, and they support the hypothesis that, despite great variability between individuals in their non-MHC background genes, human HLA-associated diseases might result from the formation of a particular ternary complex consisting of a shared MHC molecule, a common "disease-associated" epitope, and a shared TCR.
Cytokine network regulating terminal maturation of human bone marrow B cells capable of spontaneous and high rate Ig secretion in vitro.
Authors: Roldán E , Rodriguez C , Navas G , Parra C , Brieva J A 
Published: December 2022

Abstract
Human bone marrow (BM) B cells capable of spontaneous and high rate Ig secretion for 14 days in vitro have been described previously. We have shown recently that Ig secretion by these BM cells depends on stromal adherent BM cell-derived factors identified as IL-6 and fibronectin. Our report shows that the endogenous generation of IL-1 beta and TNF-alpha in serum-containing cultures of BM mononuclear cells (BMMC) is also involved in the control of Ig-secreting cells, because their blockade with specific antibodies markedly reduced Ig production. Further experiments revealed that IL-1 beta and TNF-alpha acted by regulating IL-6 production, as can be deduced from the following findings: 1) the inhibition of Ig secretion caused by either anti-IL-1 beta or anti-TNF-alpha antibodies could be reversed by exogenous IL-6; 2) the addition of either of these antibodies inhibited endogenous IL-6 production in BMMC cultures; 3) IL-1 beta plus TNF-alpha, but neither one alone, restored complete IL-6 and Ig production by BMMC in serum-free cultures. Moreover, adherent, but not nonadherent, BM cells were responsible for endogenous IL-1 beta and TNF-alpha secretion. Finally, IL-1 beta plus TNF-alpha induced the production of IL-6, but not of Ig, by adherent BM cells. Neither IL-6 nor Ig production was induced by adding this cytokine combination to nonadherent BM cell cultures, despite the fact that this fraction contained all the Ig-secreting cells. However, the addition of IL-6 restored Ig secretion in this cell fraction. These results suggest that IL-1 beta and TNF-alpha produced by adherent BM cells synergistically induce early IL-6 generation, which, in turn, drives BM B cell producers into the high rate Ig-secreting state.
IFN increases class I MHC antigen expression on adenovirus-infected human cells without inducing resistance to natural killer cell killing.
Authors: Routes J M 
Published: December 2022

Abstract
It has been previously shown that unstimulated NK cells cannot preferentially lyse adenovirus serotypes 2 and 5-infected human cells. In this study, the ability of IFN to promote the selective NK cell-mediated lysis of adenovirus-infected human cells was determined. The relationship between target cell susceptibility to NK cell-mediated killing and class I Ag expression was also analyzed through the use of adenovirus serotype 2 and 5 mutants that do not make the adenovirus early region 3 19-kDa class I binding protein. IFN induced the selective lysis of adenovirus serotype 2 and 5-infected human cells by activating NK cells (IFN-alpha) and protecting uninfected, but not adenovirus-infected cells, from NK cell-mediated lysis (IFN-gamma). IFN-gamma increased the expression of class I Ag on the surface of cells infected with the adenovirus early region 3 deletion mutants, dl327 or dl801, to a level equal to or greater than that expressed on uninfected cells. Despite the increased expression of class I Ag, IFN-gamma could not protect these adenovirus-infected cells from NK cell-mediated lysis. Thus, dl327 or dl801 infection prevented IFN-gamma's induction of cytolytic resistance to NK cell-mediated killing but left IFN-gamma's induction of class I Ag intact. Surface class I Ag levels were substantially higher on IFN-gamma-treated, dl327-, and dl801-infected cells in comparison to cells infected with wild type adenovirus serotype 5. Again, higher target cell levels of class I Ag did not correlate with increased resistance to NK cell-mediated lysis because there was equivalent NK cell-mediated killing of IFN-gamma-treated adenovirus serotype 5-, dl327-, or dl801-infected cells. Thus, IFN-gamma only protects uninfected cells from NK cell-mediated killing, irrespective of target class I Ag levels, and thereby concentrates NK lytic activity on just adenovirus-infected cells. These data demonstrate that IFN-gamma's ability to protect target cells from NK cell-mediated cytolysis is unrelated to IFN-gamma's induction of surface class I MHC Ag.
Immunogenic properties of multiple antigen peptide systems containing defined T and B epitopes.
Authors: Chai S K , Clavijo P , Tam J P , Zavala F 
Published: December 2022

Abstract
Immunization with chemically defined synthetic polymers, multiple Ag peptide (MAP) systems, containing T and B epitopes of the circumsporozoite protein of P. berghei induce high levels of circulating antibodies that are detectable several months after boosting. The anti-MAP secondary antibody response is characterized by an increase in the levels of circulating IgG and a concomitant decrease in the IgM levels. In vitro and in vivo experiments indicated that Th epitopes included in the MAP are recognized by T cells induced after immunization with the native protein and, also, that MAP-induced T cells can recognize the native protein. In addition to high levels of anti-B epitope antibodies, MAP immunization also induces antibodies against the T epitope. This anti-T epitope immune response does not affect the generation of the anti-B epitope antibodies. Immunization of different strains of mice revealed that the antibody response is consistent with the genetically restricted pattern of recognition of the T epitope. There are, however, significant differences in the levels of antibody responses observed among responder strains. The findings of this study indicate that MAP are potent immunogens capable of inducing immunologic memory and are, thus, good candidates for the development of subunit vaccines designed to induce high levels of circulating antibodies.
Translation and granule localization of mouse mast cell protease-5. Immunodetection with specific antipeptide Ig.
Authors: McNeil H P , Frenkel D P , Austen K F , Friend D S , Stevens R L 
Published: December 2022

Abstract
An antibody to mouse mast cell protease-5 (MMCP-5) was obtained by immunizing a rabbit with a 17-residue synthetic peptide corresponding to the unique amino acid sequence at residues 146 to 162 in this serine protease. After affinity purification, anti-MMCP-5(146-162) Ig reacted in SDS-PAGE immunoblots to recombinant MMCP-5 and to the native MMCP-5 protein present in the lysates of mouse serosal mast cells and the MC5 line of Kirsten sarcoma virus-immortalized mouse mast cells. Immunocytochemical staining localized MMCP-5 to the cytoplasmic granules of serosal mast cells and Kirsten sarcoma virus-immortalized mouse mast cells. Because mouse bone marrow-derived mast cells express abundant amounts of MMCP-5 mRNA, anti-MMCP-5(146-162) Ig was used to study the translation and granule accumulation of this protease when progenitor cells differentiate into these immature mouse mast cells. Maximal expression of MMCP-5 mRNA occurred after bone marrow cells had been cultured for 2 wk in IL-3-rich WEHI-3 cell conditioned medium, and MMCP-5 protein was detected in these cells. However, electron-microscopic analysis with gold-labeled antibody revealed that the amount of MMCP-5 in the individual granules of bone marrow-derived mast cells varied. The highest concentration of MMCP-5 was found in the most electron-dense secretory granules of the cells. These studies demonstrate the ultrastructural localization of the earliest transcribed mouse mast cell chymase, MMCP-5, and its granule accumulation during the differentiation of mouse bone marrow progenitor cells into immature mouse mast cells.
Importance of endothelial VCAM-1 for inflammatory leukocytic infiltration in vivo.
Authors: Pelletier R P , Ohye R G , Vanbuskirk A , Sedmak D D , Kincade P , Ferguson R M , Orosz C G 
Published: December 2022

Abstract
The microvascular endothelia of rejecting DBA/2----C57B1/6 murine cardiac allografts develop reactivity with the mAb M/K-2, which recognizes the murine homologue of the human leukocyte adhesion molecule VCAM-1. This reactivity does not develop in DBA/2----DBA/2 cardiac isografts or normal DBA/2 cardiac tissues. To determine whether endothelial VCAM-1 plays a role in allograft inflammation, cardiac allograft recipients were treated with M/K-2 antibody and monitored for leukocytic graft infiltration and graft survival. Treatment of the graft recipients with 200 micrograms/day M/K-2 Ig prolonged graft survival by 5 to 6 days (statistically significant); whereas treatment with 100 micrograms M/K-2 Ig every other day after transplant did not influence graft survival. Neither treatment interfered with leukocytic infiltration, as detected histologically or by limiting dilution analysis. The high dose treatment, but not the low dose treatment, resulted in high circulating levels of M/K-2, as detected by serum ELISA, and prominent antibody deposition on the graft vascular endothelia, as demonstrated by immunohistologic analysis. These data demonstrate that VCAM-1 is uniquely expressed on the vascular endothelia of rejecting murine cardiac allografts, and that a mAb to VCAM-1 can interfere with the allograft rejection process. Although this antibody can interfere with lymphocyte-endothelial adhesion in vitro, it has little effect on leukocytic infiltration in rejecting allografts suggesting that this process does not depend exclusively on VCAM-1 expression.
Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery.
Authors: Kennedy M K , Torrance D S , Picha K S , Mohler K M 
Published: December 2022

Abstract
Experimental autoimmune encephalomyelitis (EAE) serves as an important animal model for understanding the events that lead to immune-mediated inflammation and tissue destruction within the central nervous system. We have utilized a murine adoptive transfer model of EAE and semiquantitative reverse transcriptase-polymerase chain reaction analysis to examine cytokine mRNA expression within the central nervous system in relation to the onset and resolution of paralysis associated with EAE. Spinal cord samples, obtained from mice as they progressed through discrete clinical stages of EAE, were examined for the expression of six cytokine genes (IL-1 alpha, IL-2, IL-4, IL-6, IL-10, and IFN-gamma). Distinct patterns of cytokine gene expression were observed during the acute, recovery, and chronic phases of EAE. The acute phase of disease was characterized by rapid increases in the levels of mRNA for IL-2, IL-4, IL-6, IFN-gamma, and IL-1 alpha. In fact, peak expression of several cytokine mRNA (e.g., IL-2, IL-4, IL-6, and IFN-gamma) occurred before the peak in clinical severity. In contrast, IL-1 alpha mRNA levels were elevated throughout the initial disease course. IL-10 mRNA demonstrated only modest increases during the acute phase of EAE. Stabilization of the clinical symptoms was characterized by rapid declines in the mRNA levels of IL-2, IL-4, IL-6, and IFN-gamma. The decreases in these four cytokine mRNA levels occurred concomitant with a dramatic rise in IL-10 mRNA. Finally, of the six cytokine mRNA examined, only IL-1 alpha, IFN-gamma, and IL-10 mRNA remained elevated during the early chronic stage. These results suggest that local cytokine production varies significantly during the course of EAE and that increases in discrete sets of cytokines are associated with the acute response and the recovery/chronic phase of disease.
Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A.
Authors: Nomoto K , Eto M , Yanaga K , Nishimura Y , Maeda T , Nomoto K 
Published: December 2022

Abstract
In a murine strain combination identical in H-2 Ag but disparate in minor histocompatibility (H) Ag consisting of C3H/He (C3H; H-2k, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, a permanent skin allograft tolerance can be achieved by the cyclophosphamide (CP)-induced tolerance system that consists of i.v. injection of donor spleen cells (day -2) and i.p. injection of CP 2 days later (day 0). Such permanent take of allografts in CP-induced tolerant mice was interfered with by intramuscular injection of cyclosporin A (CsA) from day -5 to day -1 and their grafts were rejected by 21 days after grafting. Mls-1a-reactive CD4+V beta 6+ T cells in the periphery, as the indicator to follow the kinetics of donor-reactive T cells, increased on day 0 and day 3 in the C3H mice treated with AKR spleen cells alone, whereas they disappeared rapidly from day 0 to day 3 in CP-induced tolerant mice. When CsA capable of interfering with IL-2 production and T cell proliferation was administered before CP treatment in CP-induced tolerance system, the number of CD4+V beta 6+ T cells in periphery did not increase on day 0 and 3, but increased on day 7 in contrast to the decreased number of those in CP-induced tolerant mice. On day 7, MLR against donor cells was decreased in CP-induced tolerant mice, but maintained in CsA-interfered tolerant mice. These result may indicate that the destruction of donor-Ag-stimulated, proliferating T cells by CP is interfered with by CsA, probably because CsA inhibits the proliferation of donor-reactive T cells at the time of CP treatment. Furthermore, these results also implicate that the protocol for immunosuppression with CsA and antimetabolites has to be designed carefully in clinical transplantation.
Macrophage arginine metabolism and the inhibition or stimulation of cancer.
Authors: Mills C D , Shearer J , Evans R , Caldwell M D 
Published: December 2022

Abstract
The potential of the immune system to inhibit or stimulate tumor growth is a vivid example of the "two-edged sword" nature of immune responses. Our results provide evidence that this dual capacity can be attributed, in part, to the dual pathways of arginine metabolism exhibited by intratumor macrophages. Specifically, i.p. tumor rejection in P815-preimmunized mice is accompanied by an upshift in intratumor macrophage arginine metabolism to the nitric oxide (NO) synthase pathway that yields citrulline and NO. A rapid and marked local increase in IFN-gamma (both mRNA and protein) in preimmunized mice during tumor rejection suggests that this cytokine plays a role in up-regulating nitric oxide production in vivo. Unlike tumor rejection, progressive i.p. P815 tumor growth in naive mice is associated with a marked decline in the production of citruline/NO by intratumor macrophages. Examination of macrophage arginine metabolism via arginase revealed a pattern opposite that of NO synthase. The local production of ornithine/urea markedly increases during progressive tumor growth whereas arginase activity decreases during tumor rejection. Inasmuch as nitric oxide inhibits tumor cell replication whereas ornithine is the precursor of polyamines required for cell replication, these results are consistent with the conclusion that the pathway macrophages use to metabolize arginine can influence the type of host immune responses against cancer and other conditions.
Regulation of paf-acether receptor expression in human B cells.
Authors: Nguer C M , Pellegrini O , Galanaud P , Benveniste J , Thomas Y , Richard Y 
Published: December 2022

Abstract
Paf-acether (paf) is a phospholipid cytokine alloted with potent inflammatory and immunoregulatory properties. Recent reports indicated that in human B cell lines, paf modulated both early and late activation events. In our study, we showed that four of six human B cell lines specifically bound [3H]paf irrespective of the stage of differentiation, the presence of EBV genome or cell surface phenotype. Binding was saturated and fit a one receptor model with a dissociation constant ranging from 1 to 6 nM and a number of sites per cell ranging from approximately equal to 4000 in Rjc13 to approximately equal to 30,000 in Raji or IM9. In addition, our data indicate that 1) maximal expression occurred during the log phase growth; 2) paf itself (10-100 nM) or rIL-4 (100 U/ml) up-regulated by two- to threefold the number of paf binding sites without affecting the affinity. Finally, we found that activated normal B lymphocytes exhibited a higher capacity than resting B cells to incorporate and metabolize [3H]paf at 37 degrees C. Resting B lymphocytes lacked specific binding capacity for paf, yet specific paf receptors were induced upon stimulation via Staphylococcus aureus Cowan I or phorbol 12,13 dibutyrate plus ionomycin. These results suggest that B cell activation is a critical event for paf receptor expression and modulation.
Expression of the 50-kDa integrin-associated protein on myeloid cells and erythrocytes.
Authors: Rosales C , Gresham H D , Brown E J 
Published: December 2022

Abstract
Integrin-associated protein (IAP) is a 50-kDa intrinsic membrane protein that is involved in signal transduction during neutrophil activation by a variety of Arg-Gly-Asp-containing ligands. However, IAP does not itself directly bind these ligands, which are instead recognized by the leukocyte response integrin (LRI). In fact, IAP is more widely expressed than the LRI and is even on erythrocytes, which express no known integrins. This suggests that IAP may have additional functions besides signal transduction in association with the LRI. In this work we have quantitated IAP expression on several myeloid cells and cell lines, as well as erythrocytes, using a mAb which recognizes this protein. These data show that there are about 10,000 IgG-binding sites on each erythrocyte and 20 times that number on the myeloid cell lines U937 and HL60. Normal PMN and monocytes express about 25,000 IgG-binding sites. There are twice as many Fab'-binding sites on each cell, suggesting that each IgG binds via both Ag-combining sites. Binding data using several mAb to IAP suggest that IAP undergoes a temperature-dependent conformational change. Unlike some integrin receptors, IAP is not stored in a regulated secretory compartment in polymorphonuclear leukocytes (PMN). In addition, there is no evidence for internalization or shedding of IAP upon PMN activation. These data show that IAP is expressed at significant levels on myeloid cells and erythrocytes and that its expression is unaffected by the state of PMN activation.