bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-dependent induction of protective anti-influenza immune responses in human peripheral blood lymphocyte/SCID mice.
Authors: Albert S E , McKerlie C , Pester A , Edgell B J , Carlyle J , Petric M , Chamberlain J W 
Published: December 2022

Abstract
The human (hu) PBL/SCID mouse model has the potential to provide a powerful tool for the study of human immune function. However, at peak engraftment (4-8 wk postinjection), recovered human T cells are largely unresponsive to foreign Ag and have converted to an activated/memory-type phenotype. Here we show that this conversion is not a prerequisite for engraftment because at early stages (2 wk) a substantial fraction of human T cells detected in SCID peripheral blood retains the unactivated/naive phenotype of donor PBL. This early stage is also associated with a TCR repertoire in both the CD4 and CD8 subsets that is similar to that in the donor. Importantly, we show that strong HLA class I allele- and peptide-specific cytotoxic T lymphocyte as well as humoral responses can be generated in this model when human cells encounter Ag (infection with influenza A) at early, but not late, stages in engraftment. This early human response was also functional, as partial protection against influenza-induced pathology and death in SCIDs was observed. Taken together, these results demonstrate that the huPBL/SCID model can support the generation of potent and specific CTL and humoral responses provided that Ag is introduced early, presumably before the time-dependent generalized xenoactivation of engrafted human cells.
The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis.
Authors: Keane M P , Arenberg D A , Lynch J P , Whyte R I , Iannettoni M D , Burdick M D , Wilke C A , Morris S B , Glass M C , DiGiovine B , Kunkel S L , Strieter R M 
Published: December 2022

Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal disorder. Fibroplasia and deposition of extracellular matrix are dependent, in part, on angiogenesis. We postulated that an imbalance exists in the expression of angiogenic (IL-8) vs angiostatic (IFN-gamma-inducible protein (IP-10)) CXC chemokines, which favors net angiogenesis in IPF. To test this hypothesis, we obtained open lung biopsies either from normal patients undergoing thoracic surgery for reasons other than interstitial lung disease (control) or from patients with IPF. We found that levels of IL-8 were greater from tissue specimens of IPF patients then from those of controls. In contrast, IP-10 levels were higher from tissue specimens obtained from control subjects than from those from IPF patients. When IL-8 or IP-10 was depleted from IPF tissue specimens, tissue-derived angiogenic activity was markedly reduced or enhanced, respectively. Immunolocalization of IL-8 demonstrated that the pulmonary fibroblast (PF) of IPF lung was the predominant cellular source of IL-8. Isolated PF from IPF patients constitutively produced more IL-8 and less IP-10 than control PF. Conditioned media from IPF-PFs demonstrated constitutive angiogenic activity that was attributable, in part, to IL-8. Depletion of IP-10 from IPF-PF CM resulted in an increase in corneal neovascularization. These findings support the notion that IL-8 and IP-10 are important factors that regulate angiogenic activity in IPF.
Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the principal intermediate in IFN-gamma-induced suppression of exocytosis.
Authors: Eastmond N C , Banks E M , Coleman J W 
Published: December 2022

Abstract
IFN-gamma regulates various aspects of rodent peritoneal mast cell function, including mediator release, cell growth, TNF-alpha-mediated cytotoxicity, and MHC class II expression. We investigated whether the suppressive action of IFN-gamma on IgE/Ag-mediated degranulation of mast cells is mediated via synthesis of nitric oxide. Incubation of mouse peritoneal cells with L-NMMA, an inhibitor of nitric oxide synthase, or in medium lacking the nitric oxide precursor L-arginine reversed the inhibitory effect of IFN-gamma on Ag-induced serotonin release. Furthermore, the nitric oxide donors sodium nitroprusside and S-nitrosoglutathione inhibited degranulation, and this effect was direct, since it was seen equally on purified and unfractionated mast cells and occurred independently of IFN-gammaR expression. Additional experiments revealed that accessory cells in peritoneal cell populations were the principal target for the action of IFN-gamma and the main source of nitric oxide; the cytokine was more potent on unfractionated compared with purified mast cells, and IFN-gamma induced detectable nitrite production in mixed peritoneal cells, but not in purified mast cells. These studies show that IFN-gamma induces nitric oxide production in peritoneal cell populations, and that synthesized nitric oxide directly inhibits the IgE-mediated secretory function of mast cells. The activation of nitric oxide-producing cells in the tissue microenvironment may be important in the control of mast cell-dependent allergic reactions.
Eotaxin-induced eosinophil migration in the peritoneal cavity of ovalbumin-sensitized mice: mechanism of action.
Authors: Das A M , Flower R J , Perretti M 
Published: December 2022

Abstract
Cell accumulation in response to i.p. administration of the C-C chemokine, eotaxin, was studied in vivo. OVA-sensitized mice, exhibiting blood eosinophilia, had greater eosinophil (Eø) accumulation in response to 500 ng of eotaxin at 6 h (vehicle-injected, 3.0 +/- 0.5 x 10(5); eotaxin-injected, 8.6 +/- 1.0 x 10(5)) than nonsensitized, eotaxin-injected mice (2.5 +/- 0.4 x 10(5)). A nonspecific neutrophil migration was observed in both vehicle- and eotaxin-injected cavities. The number of intact mast cells in the peritoneal lavages after eotaxin injection was significantly lower than that in vehicle-injected animals (0.8 +/- 0.3 x 10(4) vs 2.8 +/-0.6 x 10(4), respectively). When endogenous peritoneal mast cells were depleted with compound 48/80 before eotaxin administration, there was a 51% reduction in Eø accumulation. This suggests an important role for endogenous mast cells in mediating the actions of eotaxin. The potential role of mast cell mediators in the actions of eotaxin was also investigated. Pretreatment with histamine-H1 or serotonin antagonists reduced Eø migration in response to eotaxin by 50 to 65%. Further, following pretreatment with a specific mAb against TNF-alpha, only nonspecific neutrophil influx was attenuated. Using neutralizing mAbs, Eø migration was found to be dependent on the adhesion molecules P- and E-selectin and CD11b. Eø accumulation was also sensitive to dexamethasone, with doses as low as 0.2 mg/kg inducing 100% inhibition. This study provides useful insight into the mechanisms of action of eotaxin.
Recombinant guinea pig and human RANTES activate macrophages but not eosinophils in the guinea pig.
Authors: Campbell E M , Proudfoot A E , Yoshimura T , Allet B , Wells T N , White A M , Westwick J , Watson M L 
Published: December 2022

Abstract
To characterize the biologic activities of potential mediators of allergic inflammation, we have cloned, expressed, and purified guinea pig RANTES (gpRANTES). cDNA for gpRANTES was cloned from Con A-stimulated guinea pig spleen cells. A high level of gpRANTES expression in Escherichia coli was achieved by mutation of a human RANTES (hRANTES) expression construct to obtain a 68-amino acid protein identical with the predicted guinea pig amino acid sequence, assuming an equivalent amino terminus as the human protein. Purified gpRANTES was an effective stimulus of human eosinophils as assessed by increases in intracellular free calcium in fura-2-loaded cells and chemotactic responses in vitro. gpRANTES exhibits similar potency and efficacy to hRANTES. In marked contrast, neither gpRANTES nor hRANTES was able to activate guinea pig peritoneal eosinophils in these assays, even in the presence of IL-5. However, gpRANTES was found to be a potent stimulator of guinea pig peritoneal macrophages. Following tracheal instillation of gpRANTES, a dose-dependent increase in macrophages, but not eosinophils, was observed in gpBAL. Macrophage accumulation was detectable by 6 h and sustained for at least 48 h. These results indicate that RANTES in the guinea pig may have a different cellular selectivity than that described in the human, which may be important in the use of animal models in the analysis of allergic disorders. These selectivities do not appear to be accounted for by differences in guinea pig and human RANTES sequences.
T cells bearing Vbeta8 are preferentially infected with exogenous mouse mammary tumor virus.
Authors: Upragarin N , Nishimura H , Wajjwalku W , Ando Y , Nagafuchi S , Watanabe T , Yoshikai Y 
Published: December 2022

Abstract
We previously reported that a mouse mammary tumor virus (MMTV(II-TES14)), encoding a superantigen specific for TCR Vbeta14, can infect lymph node (LN) cells of mice in an I-E-independent manner. Here we examined the kinetics of cell types infected with exogenous MMTV in the draining LN after s.c. injection of II-TES milk containing MMTV(II-TES14). The infectivity was assessed in LN cells sorted into each cell subset by a semiquantitative analysis of MMTV provirus using PCR with a primer specific for MMTV(II-TES14). Only B cells in the LN were infected by the MMTV on day 6 after injection, but CD8+ T cells and, to a lesser extent, CD4+ T cells were also found to be detectably infected on day 14 after the injection of II-TES milk. Among the T cells we examined, Vbeta8 T cells were most preferentially infected with MMTV, but no Vbeta14 T cells specific for MMTV(II-TES14) superantigen were infected on day 14 after infection. The transfer of Vbeta8 T cells sorted from mice injected with II-TES milk 14 days previously resulted in the deletion of CD4+ Vbeta14 T cells and in the MMTV infection of normal B6 mice. No MMTV infection of T cells occurred in IgM knockout mice, which lack a mature B cell compartment. These results suggest that MMTV surviving in B cells is transferred to Vbeta8 T cells, which may play an important role in MMTV longevity.
Antibodies against sialophorin (CD43) enhance the capacity of dendritic cells to cluster and activate T lymphocytes.
Authors: Fanales-Belasio E , Zambruno G , Cavani A , Girolomoni G 
Published: December 2022

Abstract
CD43 is a leukocyte membrane glycoprotein rich in negatively charged sialic acid residues that may act as an anti-adhesion molecule. In this study, we analyzed the expression and function of CD43 on epidermal Langerhans cells (LC) and dendritic cells derived from adherent peripheral blood monocytes treated with granulocyte-macrophage CSF and IL-4 (Mo-DC). Both freshly isolated LC (fLC) and Mo-DC expressed uniformly high amounts of membrane CD43, with levels unchanged in 48-h cultured LC or in TNF-alpha-treated Mo-DC. When fLC or Mo-DC were transiently preincubated with anti-CD43 mAb or neuraminidase, they formed much larger clusters with T cells as compared with cells incubated with control mAb. Moreover, a significantly increased proliferation of naive allogeneic T cells in a primary MLR assay was induced. Anti-CD43-treated Mo-DC also presented tetanus toxoid to primed T cells more efficiently. Immunofluorescence and immunogold electron microscopy showed that following Ab cross-linking and warming to 37 degrees C, CD43 is progressively removed from the cell surface and is internalized within endosomes and vacuoles. In addition, fLC and Mo-DC incubated with anti-CD43 mAb increased expression of HLA-DR, ICAM-1, B7-1, B7-2, CD40, and CD83 after 24 h, and this was partially prevented by culturing cells in the presence of cycloheximide. We thus postulate that membrane CD43, other than serving as anti-adhesion molecule, can mediate activation signals in immature DC, leading to augmented expression of adhesion/costimulatory molecules and Ag-presenting function.
Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice.
Authors: Pulendran B , Lingappa J , Kennedy M K , Smith J , Teepe M , Rudensky A , Maliszewski C R , Maraskovsky E 
Published: December 2022

Abstract
We have recently shown that Flt3 ligand administration dramatically increases dendritic cell (DC) numbers in various mouse tissues. This has enabled the identification of distinct mature DC subpopulations. These have been designated: population C (CD11c(bright) CD11b(bright)), D (CD11c(bright) CD11b(dull)), and E (CD11c(bright) CD11b(negative)) This report demonstrates that the mature DC subsets (C, D, and E) from Flt3 ligand-treated mice differ with respect to phenotype, geographic localization, and function. The myeloid Ags CD11b, F4/80, and Ly-6C are predominantly expressed by population C, but not D or E. In addition, a subset of population C-type DC expresses 33D1 and CD4. In contrast, DC within population D and E selectively express the lymphoid-related DC markers CD8alpha, DEC 205, CD1d, as well as CD23, elevated levels of CD117 (c-kit), CD24 (HSA), CD13, and CD54. Immunohistology indicates that the different DC subsets reside in distinct microenvironments, with populations D and E residing in the T cell areas of the white pulp, while DC within population C localize in the marginal zones. These DC subpopulations showed different capacities to phagocytose FITC-zymosan and to secrete IL-12 upon stimulation with Staphylococcus aureus cowan I strain + IFN-gamma + granulocyte-macrophage-CSF. Population C-type DC were more phagocytic but secreted little inducible IL-12 while population D- and E-type DC showed poor phagocytic capacity and secreted considerably higher levels of IL-12. These results underscore the importance of viewing DC development in vivo, as an interplay between distinct lineages and a maturational dependence on specific microenvironmental signals.
Regulation of tissue inhibitor of metalloproteinase-1 in fibroblasts and acute phase proteins in hepatocytes in vitro by mouse oncostatin M, cardiotrophin-1, and IL-6.
Authors: Richards C D , Kerr C , Tanaka M , Hara T , Miyajima A , Pennica D , Botelho F , Langdon C M 
Published: December 2022

Abstract
Mouse oncostatin M (mOSM) has been recently cloned; however, its full spectrum of biologic functions has not been defined. To assess its potential role in inflammation, we have tested the activity of mOSM in vitro in regulation of fibroblasts and hepatic cells. At concentrations of 10 and 20 ng/ml, mOSM stimulates tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in NIH-3T3 mouse embryonic fibroblasts, rat lung fibroblasts, and rat synovial fibroblasts, whereas mouse cardiotrophin-1 (mCT-1) or human OSM (hOSM) did not. Similarly, only mOSM was able to induce transcription of chloramphenicol acetyl-transferase (CAT) in NIH-3T3 cells transfected with a minimal TIMP-1 promoter/CAT construct. Mouse OSM had strong action inducing primary rat hepatocyte cultures to produce acute phase proteins; however, mOSM was very weak in its ability to stimulate acute phase protein synthesis in rat H35 cells or human HepG2 cells, which was consistent with weak STAT activation in H35 cells and HepG2 cells. Binding studies showed that NIH-3T3 cells possessed high affinity binding sites for mOSM, but rat H35 cells did not. On the other hand, mCT-1 and mouse IL-6 induced strong STAT activation as well as marked increases in acute phase protein production by H35 cells. These results indicate that mOSM does not share a functional receptor with mCT-1 or hOSM in mouse and rat cells and that hOSM does not activate the putatively specific OSM receptor on mouse or rat cells. These results also suggest that mOSM is an important cytokine in inflammation, through modulation of fibroblast function as well as hepatocyte responses.
Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99.
Authors: Ausubel L J , Krieger J I , Hafler D A 
Published: December 2022

Abstract
Myelin basic protein (MBP)-specific T cells were isolated directly from peripheral blood by stimulation either with native MBPp85-99 or altered peptide ligands (APLs) in which substitutions of the lysine were made at position 93, a TCR contact residue. We report here that the APL 93A could alter the cytokine profile of some autoreactive MBPp85-99 reactive T cell clones, switching them from a Th0 phenotype secreting high concentrations of IL-4, IL-5, and IFN-gamma into Th2 cells secreting significantly less IFN-gamma. However, in vitro stimulation with the 93A peptide, in some instances, induced T cells that responded better to the native MBPp85-99 peptide. Functionally, the APL 93A was shown to act as an antagonist for IFN-gamma secretion. Based on TCR sequencing and single cell cloning, this alteration in cytokine profile was determined to be the result of the differential activation of individual T cell clones. We discuss the implications of these data for the strength of signal model of T cell activation.
Isolation and characterization of Exodus-2, a novel C-C chemokine with a unique 37-amino acid carboxyl-terminal extension.
Authors: Hromas R , Kim C H , Klemsz M , Krathwohl M , Fife K , Cooper S , Schnizlein-Bick C , Broxmeyer H E 
Published: December 2022

Abstract
Chemokines are a group of small, homologous proteins that regulate leukocyte migration, hemopoiesis, and HIV-1 absorption. We report here the cloning and characterization of a novel murine and human C-C chemokine termed Exodus-2 for its similarity to Exodus-1/MIP-3alpha/LARC, and its chemotactic ability. This novel chemokine has a unique 36 or 37 (murine and human, respectively) amino acid carboxyl-terminal extension not seen in any other chemokine family member. Purified recombinant Exodus-2 was found to have two activities classically associated with chemokines: inhibiting hemopoiesis and stimulating chemotaxis. However, Exodus-2 also had unusual characteristics for C-C chemokines. It selectively stimulated the chemotaxis of T-lymphocytes and was preferentially expressed in lymph node tissue. The combination of these characteristics may be a functional correlate for the unique carboxyl-terminal structure of Exodus-2.
Low affinity of cell surface lymphocyte function-associated antigen-1 (LFA-1) generates selectivity for cell-cell interactions.
Authors: Ganpule G , Knorr R , Miller J M , Carron C P , Dustin M L 
Published: December 2022

Abstract
We examined binding of soluble intercellular adhesion molecule-1 (ICAM-1) dimers and a range of ICAM-1-coated particles to activated T cells. Lymphocyte function-associated antigen-1 (LFA-1) on the surface of activated T cells did not bind soluble ICAM-1 dimers with high affinity. In contrast, activated T cells adhered avidly to ICAM-1-coated planar surfaces. Between these two extremes, a range of ICAM-1-bearing particles was tested for binding. Activated T cells bound particles of 1-microm diameter or larger, but did not bind particles of 0.5-microm diameter or smaller. This threshold was eliminated, and all forms of ICAM-1 bound to LFA-1 when LFA-1 was converted to a high affinity form with an activating antibody. We show that high affinity LFA-1 is generated only as a consequence of an initial low affinity interaction of LFA-1 with ICAM-1 under physiological conditions. Therefore, the selectivity of cell surface LFA-1 for cell-sized particles bearing ICAM-1 appears to be due to the maintenance of low affinity LFA-1 on the surface of activated T cells. These findings alter the definition of inside-out signaling for LFA-1.
Early neutralizing antibody response against mouse mammary tumor virus: critical role of viral infection and superantigen-reactive T cells.
Authors: Luther S A , Maillard I , Luthi F , Scarpellino L , Diggelmann H , Acha-Orbea H 
Published: December 2022

Abstract
Infectious mouse mammary tumor virus (MMTV) is a retrovirus that expresses a superantigen shortly after infection of B cells. The superantigen first drives the polyclonal activation and proliferation of superantigen-reactive CD4+ T cells, which then induce the infected B cells to proliferate and differentiate. Part of the MMTV-induced B cell response leads to the production of Abs that are specific for the viral envelope protein gp52. Here we show that this Ab response has virus-neutralizing activity and confers protection against superinfection by other MMTV strains in vivo as soon as 4 to 7 days after infection. A protective Ab titer is maintained lifelong. Viral infection as well as the superantigen-induced T-B collaboration are required to generate this rapid and long lasting neutralizing Ab response. Polyclonal or superantigen-independent B cell activation, on the contrary, does not lead to detectable virus neutralization. The early onset of this superantigen-dependent neutralizing response suggests that viral envelope-specific B cells are selectively recruited to form part of the extrafollicular B cell response and are subsequently amplified and maintained by superantigen-reactive Th cells.
Heterogeneity of biologic responses of melanoma-specific CTL.
Authors: Fonteneau J F , Le Dréan E , Le Guiner S , Gervois N , Diez E , Jotereau F 
Published: December 2022

Abstract
To better understand how Ag density influences the various biologic responses of CTL, we analyzed lysis and, at the single cell level, cytokine production by a panel of melanoma-specific CTL clones. Titration experiments done with peptide-pulsed TAP-deficient T2 cells indicated that: 1) Ag density affects both the fraction of responding cells and the amount of cytokine secreted by each cell. 2) Different responses have a relative Ag requirement that may vary between clones. Lysis and secretion of IFN-gamma, and for most clones' secretion of TNF-alpha, required lower Ag densities, by one or two logs, than IL-2 and granulocyte-macrophage CSF secretion. 3) In a significant fraction of IFN-gamma-secreting cells, IL-2 production is not induced. 4) A large fraction of cloned cells is refractory to lymphokine gene activation for about 2 wk after previous stimulation. Together these data indicate that CTL biologic responses are controlled by variable Ag thresholds and by additional parameters affecting activation requirements of each cell. A similar heterogeneity of cytokine responses was observed to Ag endogenously presented by melanoma cells. As a consequence, most melanoma lines, including those with the highest Ag expression, could trigger only low CTL fractions to secrete IL-2 and, also for most clones, granulocyte-macrophage CSF. This may be an important component of the inefficiency of specific CTL in cancer patients.