bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syngeneic response to SJL follicular center B cell lymphoma (reticular cell sarcoma) cells is primarily in V beta 16+ CD4+ T cells.
Authors: Tsiagbe V K , Asakawa J , Miranda A , Sutherland R M , Paterson Y , Thorbecke G J 
Published: December 2022

Abstract
The growth of SJL B cell lymphomas (RCS, reticulum cell sarcoma) in vivo and in vitro is known to depend on cytokine production by RCS-responsive host CD4+ T cells. The high frequency of RCS responsive cells in normal SJL lymph nodes prompted us to prepare a set of 21 RCS-specific T cell hybridomas. Like normal SJL T cells, these hybridoma cells respond to RCS, but not to normal syngeneic B cells; produce IL-2, IL-4, and IL-5; and promote growth of RCS in gamma-irradiated syngeneic hosts. A superantigen-like stimulation by RCS cells was borne out by the fact that all the RCS-specific hybridomas used V beta 16 in their TCR. RCS cells did not stimulate I-As-restricted, V beta 17a+ KLH-specific, or V beta 1+ heme-specific hybridomas, but were excellent Ag presents for these cells. Preincubation of RCS cells with high concentrations of the KM core peptide (high affinity for I-As) did not interfere with the ability of RCS to stimulate RCS-specific hybridomas. The relative representation of mRNA for V beta 1, 4, 10, 15, 16, and 17a was evaluated in RNA extracted from normal SJL lymph node cells responding to Con A or to RCS cells. Only V beta 16 was specifically enriched in the response to RCS. Moreover, the degree of responsiveness to RCS cells in lymph node cells from F1 hybrids of SJL and I-E transgenic SJL mice, corresponds to the relative abundance of V beta 16 in mRNA, but not of V beta 17a mRNA.
IFN-gamma-mediated antimicrobial response. Indoleamine 2,3-dioxygenase-deficient mutant host cells no longer inhibit intracellular Chlamydia spp. or Toxoplasma growth.
Authors: Thomas S M , Garrity L F , Brandt C R , Schobert C S , Feng G S , Taylor M W , Carlin J M , Byrne G I 
Published: December 2022

Abstract
The role of indoleamine 2,3-dioxygenase (IDO) in IFN-gamma-mediated inhibition of intracellular parasite growth has been examined previously, although earlier work has been largely correlative. In this study, we defined more completely the role of IDO in the IFN-antimicrobial response. Two mutant cell lines, derived from ME180 cells and exhibiting reduced IDO activity (IR3B6A, IR3B6B) were characterized to determine if they retained the capacity to inhibit intracellular Chlamydia and Toxoplasma growth. Mutant cells treated with IFN-gamma exhibited reduced capacity to suppress pathogen growth. The expression of several IFN-regulated genes also was measured to confirm that the inability to inhibit pathogen growth was because of the lack of IDO. The expression of class II MHC, intracellular adhesion molecule-1, MxA, and P68 kinase genes was induced in the IFN-gamma-treated wild type ME180 cells, but was variable in the mutant cell lines, supporting the hypothesis that IFN-gamma-induced production of IDO is a key IFN-gamma-mediated antimicrobial mechanism.
Four different classes of inhibitors of receptor-mediated endocytosis decrease tumor necrosis factor-induced gene expression in human endothelial cells.
Authors: Bradley J R , Johnson D R , Pober J S 
Published: December 2022

Abstract
We have investigated the relationship between receptor-mediated endocytosis of TNF and TNF-induced gene expression in cultured human endothelial cells. Exposure of cells to hypertonicity, to cytoplasmic acidification, to treatment with phenylarsine oxide, or to treatment with primary amines such as putrescine or dansylcadaverine each inhibited receptor-mediated endocytosis by 30 to 75%, as measured by uptake of acetylated Dil-low density lipoprotein or of 125I-TNF. All four treatments also inhibited TNF-induced surface expression of ELAM-1 by 50 to 100%. Among these four treatments, only hypertonicity inhibited pinocytosis, as measured by uptake of fluorescein-BSA, and only phenylarsine oxide irreversibly inhibited protein synthesis, as measured by [35S]methionine incorporation. Notably, acidification or treatment with primary amines selectively inhibited the response to TNF, compared with the response to PMA, a drug that induces ELAM-1 through a pathway that bypasses surface receptors. Primary amines, which can be used for sustained periods under physiologic culture conditions without causing toxicity, were investigated further. Pretreatment of endothelial cells with 10 mM putrescine or 100 microM dansylcadaverine also inhibited TNF induction of ICAM-1 expression and VCAM-1 expression. Primary amines also inhibited IL-1-induced increases in ELAM-1, ICAM-1, and VCAM-1 measured 4 to 6 h after treatment and inhibited IFN-beta- and IFN-gamma-mediated induction of class I MHC molecules and IFN-gamma-mediated induction of class II MHC molecules measured 72 h after treatment with cytokine. Levels of mRNA encoding cytokine-inducible molecules were also selectively reduced by primary amines. A constitutively expressed surface molecule, gp96, was not affected in the same cells. These data are consistent with a role for receptor-mediated endocytosis in TNF-mediated gene induction and suggest a new potential target for anti-inflammatory therapy.
Expression of prolactin receptors in murine lymphoid cells in normal and autoimmune situations.
Authors: Gagnerault M C , Touraine P , Savino W , Kelly P A , Dardenne M 
Published: December 2022

Abstract
We have analyzed the expression of prolactin receptors (PRL-R) on murine lymphoid cells by using flow cytofluorometry analysis with biotinylated anti-PRL-R mAb raised against several epitopes of the extracellular domain of the PRL-R and by using polymerase chain reaction amplification. We demonstrated that PRL-R were universally expressed in normal rat and mouse hematopoietic tissues. In both primary lymphoid organs, namely, thymus and bone marrow, &gt; 90% of cells were labeled by the anti-PRL-R mAb, but the density of PRL-R (assessed by fluorescence intensity) was lower on thymocytes than on bone marrow cells. In peripheral lymphoid organs there were smaller proportions of cells bearing PRL-R and we could clearly distinguish cell subsets of various fluorescence intensities. By using classical markers for lymphoid cell populations, we noted that all B cells and macrophages from spleen, lymph nodes, and blood strongly expressed the PRL-R. Regarding T cell populations, large proportions (&gt; 85%) of PRL-R+ cells were detected in the four thymocyte subsets, thus contrasting with the smaller proportions (50 to 65%) of T cells labeled in the periphery. Similar percentages of PRL-R+ cells were observed in CD4+ and CD8+ peripheral lymphocyte subsets. Importantly, the stimulation of thymocytes and spleen cells with the T cell mitogen Con A promoted an enhancement of the density of PRL-R molecules on the cell membranes. Because hyperprolactinemia is associated with some autoimmune diseases, we also investigated PRL-R expression in the NZB autoimmune mouse. In contrast to the pattern observed in normal animals, the frequencies of PRL-R-bearing T cells as well as the density of PRL-R per cell increased with age in NZB mice, suggesting that some imbalances of PRL/PRL-R interaction might occur in autoimmune situations. In conclusion, our data provide a molecular basis for a better understanding on the mode of action of PRL within the immune system in physiologic and pathologic situations.
Characterization of T cells infiltrating the heart in rats with experimental autoimmune myocarditis. Their similarity to extrathymic T cells in mice and the site of proliferation.
Authors: Hanawa H , Tsuchida M , Matsumoto Y , Watanabe H , Abo T , Sekikawa H , Kodama M , Zhang S , Izumi T , Shibata A 
Published: December 2022

Abstract
A model of experimental autoimmune myocarditis, which resembles fatal giant cell myocarditis in humans, was previously established in rats immunized by s.c. injection of human cardiac myosin. We characterized herein the surface phenotype of lymphocytes infiltrating the heart and pericardial cavity as well as of mononuclear cells in various organs by using mAb in conjunction with immunofluorescence tests. Since profound thymic atrophy always accompanied the diseased states, attention was focused on characterization of T cells with properties similar to those of extrathymic T cells. In mice, extrathymic T cells were activated in association with thymic atrophy, expressed high levels of LFA-1 and IL-2R beta-chains, and contained a significant proportion of double negative CD4-CD8- T cells. In diseased rats, a large proportion of activated T cells that expressed high levels of LFA-1 and IL-2R was demonstrated in the pericardial effusion and heart tissue. Such T cells were rare in the other organs. Light scatter and microscopic observation revealed that activated lymphoblasts were most abundant in the pericardial effusion. Moreover, one-fourth of such T cells in the pericardial effusion displayed double negative phenotype. These cells in rats might correspond to the extrathymic T cells in mice. However, only a limited population of such activated T cells infiltrated the heart tissue. Concerning the location of such T cells mainly in the outer layer of the heart, it raised the possibility that extrathymic T cell differentiation in these autoimmune rats might occur in the pericardial cavity, and the differentiated cells then migrated to the sites of the cardiac lesion.
Religation of the T cell receptor after primary activation of mature T cells inhibits proliferation and induces apoptotic cell death.
Authors: Radvanyi L G , Mills G B , Miller R G 
Published: December 2022

Abstract
The proliferative response of murine splenic T cells, initially activated by cross-linking the TCR complex with either antibodies, mitogenic lectin, or alloantigen was severely inhibited when the activated cells were recovered and given an additional activation signal by recross-linking the TCR complex, or by adding Ca2+ ionophore and phorbol ester. Under the same conditions, cross-linking other T cell surface determinants such as CD4, CD8, or class I MHC on preactivated T cells had no effect. Assessment of cell viability using vital dye exclusion together with the detection of DNA fragmentation revealed that the reduction of the proliferative responses was associated with an induction of apoptotic-like cell death in the activated T cell population and not due to a blockade of cell division. Accumulation of eosin stained (dead) cells did not occur immediately upon replating the activated cells, but began after a lag period during which at least two cell divisions occurred. In addition, perturbation of T cell proliferation after activation depended on how the cells were initially activated. Only T cells activated in the presence of additional cells found in spleen and lymph node were susceptible to inhibition; T cells activated after nylon wool purification were not susceptible. These results have potential implications for understanding self-tolerance and immunoregulation.
Usage of T cell receptor beta-chain variable gene is highly restricted at the site of inflammation in murine autoimmune uveitis.
Authors: Rao N A , Naidu Y M , Bell R , Lindsey J W , Pararajasegaram G , Sun Y , Steinman L 
Published: December 2022

Abstract
Improved molecular methods allow identification of the specific autoaggressive T cells involved in autoimmune inflammations. In this study of interphotoreceptor retinoid-binding protein-induced uveitis, TCR V beta usage was studied using RNA-polymerase chain reaction amplification of transcripts derived directly from ocular tissues and from T cell lines obtained from the spleen. Specific V beta 5' primers from the major murine TCR V beta families were coupled with a common 3' primer from the V beta C region. Amplification of rearranged TCR V beta-D beta-J beta-C beta sequences was confirmed by Southern blot analysis. In ocular tissue from sensitized mice, TCR V beta expression was limited mainly to one to three V beta families, with predominant expression of V beta 2, V beta 12, and V beta 15. In most animals there was similar, albeit limited, TCR gene usage in both the recognition of autoantigen in uveitogenic T cell lines and at the site of inflammation in the eye. Identification of a limited TCR V beta repertoire in Ag-reactive T cell lines correlated with TCR usage at the target site of autoimmune expression. The gene products of the restricted TCR V beta rearrangements found in lesions and in the cell lines may serve as the target for selective immunotherapy.
Preferential activation of Th2 cells in chronic graft-versus-host reaction.
Authors: De Wit D , Van Mechelen M , Zanin C , Doutrelepont J M , Velu T , Gérard C , Abramowicz D , Scheerlinck J P , De Baetselier P , Urbain J 
Published: December 2022

Abstract
The injection of DBA/2 parental lymphocytes into adult, immunologically intact (C57BL/6 x DBA/2) F1 hybrid mice results in a chronic graft-vs-host reaction (GVHR) characterized by a deficiency in CD4+ T cell functions and a B cell activation leading to autoantibody production. The discovery that distinct subpopulations of Th cells may regulate the effector immune functions led us to investigate whether the chronic GVHR differentially affects Th subsets. Data are presented indicating that mice undergoing a GVHR spontaneously produced lymphokines of Th2 origin. IL-4 and IL-10 mRNA were detected in the spleens of GVH mice, and IL-4 was shown to be responsible for the increased expression of class II Ag on B cells. Moreover, upon polyclonal activation in vitro, GVH T cells exhibited defective IL-2 and IFN-gamma production but elevated IL-4 production. We conclude that the chronic GVHR is characterized by a selective deficiency in cells secreting IL-2 and IFN-gamma and a hyperactivation of Th2 cells. The simultaneous production of IL-4 and IL-10 might explain the association between B cell hyperactivity and impairment of Th1-like activities in various models that associate autoimmunity and immunosuppression, such as GVHR and HIV infection.
IgA antibodies to a protective antigen in human Schistosomiasis mansoni.
Authors: Grzych J M , Grezel D , Xu C B , Neyrinck J L , Capron M , Ouma J H , Butterworth A E , Capron A 
Published: December 2022

Abstract
The specific IgA antibody responses to the protective recombinant Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST) Ag and to derived synthetic peptides have been evaluated before and 6 mo after chemotherapy in S. mansoni-infected patients from Kenya. These studies revealed a parallelism between the age-dependent evolution of IgA antibody levels to Sm28GST and to one synthetic peptide (115-131) and the acquisition of resistance to reinfection. Functional analysis revealed that IgA antibodies to Sm28GST displayed a potent neutralizing effect on the enzymatic properties of the molecule, and also markedly impaired schistosome fecundity, by limiting both the egg laying of mature worms and the hatching capacity of schistosome eggs into viable miracidia. These results suggest that, in addition to IgE, IgA antibodies might participate in the protective immune response against schistosomiasis.
Macrophage colony-stimulating factor in human fetal astrocytes and microglia. Differential regulation by cytokines and lipopolysaccharide, and modulation of class II MHC on microglia.
Authors: Lee S C , Liu W , Roth P , Dickson D W , Berman J W , Brosnan C F 
Published: December 2022

Abstract
CSF-1 is a growth factor that selectively promotes the proliferation, survival, and differentiation of cells of the mononuclear phagocyte series. As part of a study on the role of cytokine and hematopoietic growth factors in central nervous system (CNS) development and inflammation, we examined the expression of CSF-1 in dissociated glial cells cultured from human fetal CNS tissue. CSF-1 mRNA and protein were constitutively expressed by astrocytes. The steady state level of CSF-1 mRNA was markedly up-regulated by both IL-1 beta and TNF-alpha in a time- and dose-dependent manner, whereas only a minimal increase was detected after stimulation with LPS. In unstimulated astrocyte cultures, CSF-1 protein levels gradually increased to 3.5-fold base-line values by 96 h and were significantly increased by all three stimulants in the order of IL-1 &gt; or = TNF &gt; LPS. Low levels of CSF-1 mRNA and protein were also detected in unstimulated microglia cultures. In contrast to astrocyte cultures, CSF-1 mRNA and protein increased significantly after stimulation with LPS, but changed only minimally after exposure to TNF-alpha or IL-1 beta. The effect of CSF-1 on cell proliferation, morphology, and class II MHC Ag expression was determined in highly enriched cultures of microglia and astrocytes. Microglia treated with CSF-1 showed a modest level of proliferation and differentiation into rod-shaped cells, whereas neither cell number nor shape was changed in astrocyte cultures. Interestingly, marked inhibition of both basal and IFN gamma-induced class II MHC Ag expression was observed in microglial cells cultured in the presence of CSF-1, whereas no effect was detected in astrocytes. These results suggest the possibility that in situ production of CSF-1 in the CNS may regulate normal glial cell development and contribute to the immunologic status of the CNS through the down-regulation of class II MHC expression.
Soluble E-selectin is found in supernatants of activated endothelial cells and is elevated in the serum of patients with septic shock.
Authors: Newman W , Beall L D , Carson C W , Hunder G G , Graben N , Randhawa Z I , Gopal T V , Wiener-Kronish J , Matthay M A 
Published: December 2022

Abstract
A quantitative sandwich ELISA for E-selectin in the fluid phase (soluble E-selectin, sEs) has been developed that is sensitive to 100 pg/ml. The assay shows no reactivity with either L- or P-selectins. We have used this to determine the fate of E-selectin after cell-surface expression and to test whether levels measured in vivo may represent the state of endothelial activation. E-selectin was first detectable in supernatants of IL-1-stimulated endothelial cells at 24 h, and increased slowly up until 72 h. However, over this time period the total E-selectin detectable in the system (cells plus supernatants) declined dramatically. 125I-surface-labeled endothelial cells cultured for 24 h show an E-selectin of reduced m.w. in the supernatant, indicating that the molecule is shed from the surface. The shed form also appears to be slightly smaller than the intact membrane form as determined from immunoprecipitation and molecular sieving studies. In addition, the cytoplasmic domain of the molecule found in supernatants of activated endothelial cells and in serum is not intact as determined by loss of reactivity with an antipeptide antibody specific for the cytoplasmic domain. We have examined the sera of 71 normal individuals. Without exception, sEs was found in serum in the range of 0.13 to 2.8 ng/ml, suggesting that even in the absence of overt inflammatory processes E-selectin is being synthesized and released into the bloodstream. In addition, bacteremic patients with hypotension, but not those without, showed markedly elevated sEs values. As determined by cell-binding studies, the blood-derived form of E-selectin is biologically active.
Detection and quantitation of cells secreting IL-6 under physiologic conditions in BALB/c mice.
Authors: Shirai A , Holmes K , Klinman D 
Published: December 2022

Abstract
IL-6 is a pleiotropic cytokine involved in the regulation of hematopoiesis and lymphocyte activation. An extremely sensitive ELIspot assay was developed to detect and enumerate individual cells secreting IL-6 in normal BALB/c mice. Under physiologic conditions, the frequency of cells producing IL-6 in the bone marrow, spleen, and mesenteric lymph nodes of normal adult animals was approximately 0.5, 0.1, and 0.01%, respectively. FACS analysis revealed that macrophages and Mac1- B220- cells accounted for the vast majority of IL-6 production in the bone marrow, whereas T and B lymphocytes accounted for 4% and 38% of IL-6 production in the spleen. Simultaneous studies comparing cell number with IL-6 levels indicated that the average activated cell produced approximately 85 molecules of IL-6/s.
Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma. Tumor inhibition by IL-2 but not tumor necrosis factor.
Authors: Karp S E , Farber A , Salo J C , Hwu P , Jaffe G , Asher A L , Shiloni E , Restifo N P , Mulé J J , Rosenberg S A 
Published: December 2022

Abstract
Recent investigations have demonstrated that the in vivo growth of weakly immunogenic murine tumors can be inhibited by genetic manipulations that enable them to secrete a variety of cytokines. Inasmuch as most human tumors fail to elicit a detectable host immune response we questioned whether the growth of a nonimmunogenic murine tumor could be inhibited by the secretion of cytokines. We have thus inserted the cDNA encoding for human IL-2 or TNF into the nonimmunogenic murine fibrosarcoma MCA 102. Tumor cells secreting IL-2 failed to grow in vivo despite normal in vitro growth. This growth inhibition required an intact immune system as tumors grew progressively in mice sublethally irradiated before tumor injection. Tumor inhibition was abrogated by the in vivo depletion, by specific mAb before tumor injection, of either CD8+ T cells or NK cells, but not CD4+ T cells. IL-2 secretion by tumor afforded a significant survival benefit to the animal, and IL-2-secreting tumor limited the growth of admixed nonsecreting parental tumor. Histologic evidence and FACS analyses revealed a dense lymphocytic infiltration of IL-2-secreting tumors composed of both CD4+ and CD8+ T cells. In contrast, secretion of TNF failed to inhibit the growth of MCA 102, and similar lymphocyte subset depletions, or administration of specific anti-TNF mAb had no effect on the growth of TNF secreting MCA 102. In summary, these investigations demonstrated that the host response to this nonimmunogenic tumor can be markedly enhanced by the genetic manipulation of the tumor cells to secrete IL-2, but not TNF. This strategy has potential application for the development of immunotherapies for nonimmunogenic tumors.