bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage analysis of the Bcg gene on mouse chromosome 1. Identification of a tightly linked marker.
Authors: Schurr E , Skamene E , Forget A , Gros P 
Published: December 2022

Abstract
We have mapped and determined the gene order of five cloned genes in the vicinity of the murine host resistance gene Bcg on mouse chromosome 1. For this, we have used a RFLP-type analysis in panels of 43 recombinant inbred strains, 3 congenic mouse strains, and 186 segregating backcross progeny derived from inbred strains of Bcgr and Bcgs genotypes. The Bcg alleles of segregating animals were established by in vivo infection with Mycobacterium bovis (Bacillus Calmette-Guérin) strain Montreal. Genomic DNA prepared from progenitor mouse strains was isolated, digested with restriction endonucleases, and analyzed by Southern blotting to identify strain-specific RFLP for each DNA marker tested. Among a number of DNA markers tested, Len2, Fn, Vil, Alpi, and Achrg were found to co-segregate with Bcg in mouse strains congenic for this locus. Detailed segregation analysis of the five markers and Bcg showed that Vil was extremely close to Bcg with no recombinant identified, whereas Fn and Len2 were located 4.5 and 9 cM proximal of Bcg, respectively. Alpi and Achrg mapped 5 and 5.5 cM distal from Bcg, respectively. Pedigree analysis in the recombinant inbred strains and backcross animals indicated the gene order: centromere-Len2-Fn-Vil,Bcg-Alpi-Achrg. The tightly linked Vil marker can now be used as an entry point in recombinant genomic DNA libraries to clone sequences overlapping Bcg. This group of five genes flanking Bcg on mouse chromosome 1 is precisely conserved on the telomeric end of the long arm of human chromosome 2q. Our results suggest that a likely location for a putative human homologue to the murine host resistance gene Bcg is the long arm of human chromosome 2 (2q32-qter).
Human tumor infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy.
Authors: Belldegrun A , Kasid A , Uppenkamp M , Topalian S L , Rosenberg S A 
Published: December 2022

Abstract
Tumor infiltrating lymphocytes (TIL) isolated from 12 patients with metastatic malignant melanoma, renal cell carcinoma, or breast adenocarcinoma were expanded in rIL-2 for 22 to 45 days (median 33 days) and analyzed for lymphokine mRNA expression and patterns of TCR gene rearrangement. All TIL cultures were significantly enriched for T cells, with CD3+ CD8+ cells predominant in 8 of 10 cases tested, and demonstrated an oligoclonal (rather than polyclonal) pattern of TCR gene rearrangement. Nine of 12 cultures could effectively lyse the autologous targets in short term chromium release assays. IL-2 expanded-TIL expressed mRNA for TNF-alpha and TNF-beta (lymphotoxin) and, in 5 of 9 (41%) cases, granulocyte/macrophage-colony stimulating factor mRNA but not IL-1 beta or IL-2 transcripts. Cultured TIL deprived of rIL-2 for 4 days did not constitutively express mRNA for any of the lymphokines tested. One long term TIL line in culture was followed and periodically tested for lytic activity and TNF-mRNA expression. Loss of the specific cytolytic but not proliferative activity at day 85 was associated with disappearance of TNF mRNA. Profiles of lymphokine secretion may provide a useful marker for functionally characterizing different T cell subsets and may provide correlates of the in vivo anti-tumor effects of these cells when TIL are adoptively transferred into cancer-bearing patients.
Role of tumor necrosis factor-alpha in E1A oncogene-induced susceptibility of neoplastic cells to lysis by natural killer cells and activated macrophages.
Authors: Cook J L , May D L , Wilson B A , Holskin B , Chen M J , Shalloway D , Walker T A 
Published: December 2022

Abstract
NIH-3T3 cells transfected with adenovirus E1A oncogene cDNA were found to exhibit cytolytic susceptibility to murine NK cells and activated macrophages associated with a threshold level of oncogene product expression exceeding that required for morphological transformation. A similar correlation was observed between threshold levels of E1A gene product expression and target cell susceptibility to direct cytotoxicity by rTNF. Inhibition of splenic NK cell and peritoneal macrophage cytolysis by antisera specific for murine rTNF confirmed the importance of E1A-induced TNF susceptibility as one determinant of target cell cytolytic susceptibility. Anti-TNF antibody was, however, unable to block killing of E1A-expressing targets by the NK cell line, NKB61A2. These results suggest a direct link between the functions of E1A oncogene products and cellular mechanisms of action of TNF elaborated by host effector cells and indicate that E1A expression also affects target cell susceptibility to TNF-independent cytolytic mechanisms.
Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans.
Authors: Hoffenbach A , Langlade-Demoyen P , Dadaglio G , Vilmer E , Michel F , Mayaud C , Autran B , Plata F 
Published: December 2022

Abstract
CTL specific for the HIV belong to the CD8 subset of T lymphocytes, and their activity is restricted by class I HLA transplantation Ag. In this report, HIV-specific CTL and their precursor cells were quantified by limiting dilution analysis. CTL were recovered from the lungs, lymph nodes, and blood of asymptomatic seropositive carriers and of patients with AIDS. HIV was found to be very immunogenic. High frequencies of both HIV-specific CTL and CTL precursor cells were detected in infected individuals. These CTL killed autologous HIV-infected macrophages and T4 lymphoblasts. They also killed doubly transfected P815-A2-env-LAV mouse tumor cells, which express the human HLA-A2 gene and the HIV-1 env gene. In the longitudinal studies of two HIV-infected patients, CTL and CTL precursor cell frequencies decreased as the clinical and immunologic status of the patients deteriorated. Most surprisingly, PBL from seronegative donors also responded to HIV stimulation in vitro and generated large numbers of HLA-restricted, HIV-specific CTL.
Transfusion induces blood donor-specific suppressor cells.
Authors: Quigley R L , Wood K J , Morris P J 
Published: December 2022

Abstract
Transfusion with blood from the organ donor before transplantation can prolong the survival of renal allografts in the rat. To determine if the beneficial effect of preoperative blood transfusion was due to the generation of donor-specific suppressor cells, in vivo and in vitro adoptive transfer experiments were performed. Lymphoid cells were harvested from transfused and untreated rats. These cells were then either (1) transferred to lightly irradiated (200 R) syngeneic hosts which were subsequently challenged with a kidney allograft (in vivo assay) or (2) titrated as regulator cells into naive unidirectional MLC such that the regulator and responder populations were syngeneic. In the LEW-RT1 to DA-RT1av1 strain combination, the adoptive transfer of thoracic duct lymph (TDL) or lymph node (LN) cells (5 x 10(7) to 7.5 x 10(7) cells) from DA animals transfused with LEW blood, 7 days previously into syngeneic (DA), lightly irradiated (200 R) hosts resulted in the indefinite survival of LEW kidney allografts. The phenomenon was blood donor-specific and dose-dependent. In contrast the adoptive transfer of spleen cells (10(7) to 10(8] from blood transfused hosts 7 days after transfusion had no effect on renal allograft survival. In vitro the addition of LN or TDL regulator cells, harvested from DA rats transfused with LEW blood, to a unidirectional MLC (DA responders, LEW stimulators) resulted in a significant depression of the proliferative response when compared with the proliferation of these same cells without the addition of these regulator cells or with the addition of LN or TDL regulator cells from a DA rat transfused with third party (PVG-RT1c) blood. The depression of the proliferative response observed in vitro, was blood donor specific. When LN or TDL regulator cells from a DA rat transfused with PVG-RT1c blood were added to a unidirectional MLC between DA responders and PVG stimulators, a significant depression in the proliferative response was observed. These in vitro findings were confirmed in two other strain combinations (LEW-PVG, and DA-PVG). Thus a single blood transfusion results in the induction of donor-specific suppressor cells detectable both in vivo and in vitro 7 days after transfusion in some but not all lymphoid compartments.
Organ-specific autoimmune disease induced in mice by elimination of T cell subsets. V. Neonatal administration of cyclosporin A causes autoimmune disease.
Authors: Sakaguchi S , Sakaguchi N 
Published: December 2022

Abstract
Cyclosporin A (CsA), a potent immunosuppressive drug, caused organ-specific autoimmune disease, such as gastritis with anti-parietal cell autoantibodies or oophoritis with anti-oocyte autoantibodies, in BALB/c mice when the drug was administered daily for 1 wk to newborns. Administration to adult mice did not. CsA abrogated the production of L3T4+ T cells and Lyt-2+ T cells in the thymus. Consequently, these T cells were substantially depleted from the peripheral lymphoid organs, especially when the drug was administered from the day of birth. Autoimmune disease was prevented when CsA-treated newborn mice were inoculated with splenic T cells from normal syngeneic mice. However, removal of the thymus immediately after neonatal CsA treatment produced autoimmune disease with a higher incidence and in a wider spectrum of organs, i.e., thyroiditis, sialoadenitis of the salivary gland, gastritis, insulitis of the endocrine pancreas, adrenalitis, oophoritis, or orchitis. Each autoimmune disease was accompanied by the development of circulating autoantibodies specific for the corresponding organ Ag. Immunopathology of these autoimmune diseases was quite similar to that of human organ-specific autoimmune diseases.
Binding the low affinity Fc epsilon R on B cells suppresses ongoing human IgE synthesis.
Authors: Sherr E , Macy E , Kimata H , Gilly M , Saxon A 
Published: December 2022

Abstract
Our results support the hypothesis that binding the low affinity Fc epsilon R (Fc epsilon R-II, CD23) on IgE-secreting B cells, directly suppresses IgE production. IgE production from AF-10/U266 (a human IgE plasmacytoma) decreased upon incubation with anti-IgE mAb or IgE:anti-IgE immune complexes (IgE-IC). Synthesis was suppressed a maximum of 51% with 10 micrograms/ml of IgE-IC after a 24-h incubation. Spontaneous in vitro IgE synthesis from the B cells of highly atopic individuals was also inhibited in a similar fashion. This effect was isotype specific as IgA or IgG immune complexes did not alter IgE production from AF-10 nor did IgE-IC affect IgA or IgG synthesis from lymphoblastoid cell lines making IgG (GM1500 and RPMI 8866) or IgA (GM1056). U266/AF-10 cells displayed both membrane IgE (greater than 90%) and Fc epsilon R-II (23%). To evaluate the role of these membrane proteins in the observed suppression of IgE synthesis, we treated U266/AF-10 cells with IgE-IC that bound Fc epsilon R-II but could not bind membrane IgE, as the mAb used was directed against an idiotypic determinant on the myeloma IgE (PS) used to make the IgE-IC. Suppression was maximal (greater than 50%) with these complexes at 0.1 micrograms/ml and at a 1/1 ratio of mAb anti-IgE to human myeloma IgE. When IgE-IC were used that were constructed with heat denatured IgE or F(ab')2 fragments of IgE, suppression was abrogated indicating IgE-Fc epsilon R binding was required. Neither PS IgE nor mAb 5.1 (the components of IgE-IC) alone affected IgE synthesis. Furthermore, a mAb binding directly to CD23 suppressed IgE synthesis from AF-10 up to 60%. Using limiting dilution analysis, we determined that IgE production per AF-10 cell was constant (0.9 pg/cell/24 h), independent of cell density and cells incubated with IgE-IC were uniformly suppressed. To clarify the mechanism of IgE-IC-induced suppression on AF-10 cells, we assessed both the proliferative rate and cell cycle distribution upon incubation with IgE-IC. There was no correlation between IgE production and [3H]TdR incorporation by AF-10 cells incubated with IgE-IC or anti-CD23 mAb. The distribution of cells within the cell cycle was unaffected by these treatments, with 60% of the cells in G1. These results define a direct role for the Fc epsilon R-II on B cells in the regulation of ongoing IgE synthesis.
Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines.
Authors: Faltynek C R , Finch L R , Miller P , Overton W R 
Published: December 2022

Abstract
The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.
Both granulocyte-macrophage CSF and macrophage CSF control the proliferation and survival of the same subset of alveolar macrophages.
Authors: Lin H S , Lokeshwar B L , Hsu S 
Published: December 2022

Abstract
The effect of granulocyte-macrophage (GM)-CSF on the proliferation of murine pulmonary alveolar macrophages in vitro was investigated. About 20% of freshly isolated alveolar macrophages formed colonies in both liquid and soft agar cultures in the presence of GM-CSF. GM-CSF was also found to be capable of maintaining the survival of these colony-forming cells in vitro. Moreover, GM-CSF could substitute for CSF-1 in maintaining the survival of CSF-1-responding pulmonary alveolar macrophage colony-forming cells in the absence of CSF-1. The concentration of GM-CSF required for maintaining the survival of colony-forming cells without proliferation was much lower than that required for the proliferation of these cells in vitro. It also enhanced the CSF-1-dependent clonal growth of alveolar macrophages. These data suggest that the colony-forming cells that respond to GM-CSF are the same subset of macrophages that form colonies in the presence of CSF-1. GM-CSF did not inhibit the binding of 125I-CSF-1 to alveolar macrophages at 0 degrees C. However, the preincubation of macrophages with GM-CSF at 37 degrees C resulted in a transient down-regulation of CSF-1 binding activity.
Presence of IL-1 receptors on human and murine neutrophils. Relevance to IL-1-mediated effects in inflammation.
Authors: Parker K P , Benjamin W R , Kaffka K L , Kilian P L 
Published: December 2022

Abstract
Inflammatory responses are characterized by the infiltration of polymorphonuclear neutrophils (PMN) at the involved site. IL-1 may have an important role in mediating this response, but whether IL-1 acts directly on PMN is controversial. In this study, we examined PMN for the presence of IL-1R and determined the effect of IL-1 on PMN migration in vivo. Thioglycollate, proteose-peptone, or IL-1 elicited peritoneal exudate cells were found to bind 125I-IL-1 alpha in a specific and saturable manner. This binding was localized to the PMN in the exudate. Scatchard plot analysis indicates the presence of approximately 1700 receptors per PMN and an apparent dissociation constant of 3.0 x 10(-10) M. Binding sites for 125I-IL-1 alpha were also found on human PMN prepared from peripheral blood. There are approximately 900 receptors per cell on human PMN with a dissociation constant similar to that observed for elicited murine PMN. Binding of 125I-IL-1 alpha to the mouse and human PMN is inhibited by both recombinant human IL-1 alpha and IL-1 beta, indicating that both IL-1 proteins bind to the same receptor on these cells. Human PMN were able to internalize radioiodinated IL-1. We conclude that PMN possess receptors for IL-1 and that these binding sites may be important in mediating IL-1 effects on granulocytes that are involved in the inflammatory response.
Protein kinase C-dependent and -independent mechanisms of cloned murine T cell proliferation. The role of protein kinase C translocation and protein kinase C activity.
Authors: Kim D K , Lancki D W , Hui F H , Fitch F W 
Published: December 2022

Abstract
PMA can induce the proliferation of several CTL clones but not of several Th clones derived and tested in our laboratory. The PMA-stimulated proliferation of our CTL clones (which do not make IL-2 mRNA or protein) occurs independently of IL-2 and is not accompanied by lymphokine release. We now report, however, that protein kinase C (PKC) translocation is induced by PMA in CTL clones as well as in Th clones, which lack a proliferative response to PMA. These results suggest that PKC translocation itself is not a sufficient regulatory mechanism to account for cloned T cell proliferation. Moreover, IL-2 did not induce PKC translocation in a CTL clone, which proliferates when stimulated with IL-2. Thus, PKC translocation may not be necessary for activation of CTL proliferation. Nonetheless, cellular PKC activity appears to be required for the proliferative response of T cell clones after stimulation by PMA/PMA + calcium ionophore (A23187) or by triggering through the TCR: chronic PMA treatment, which depletes intracellular PKC activity, abrogates the proliferative response of T cell clones stimulated by PMA/PMA + A23187 or triggered through the TCR. T cell clones depleted of PKC activity, however, retain the ability to proliferate when challenged with IL-2. Murine T cell clones, therefore, possess PKC-dependent and PKC-independent pathways of proliferation that are not regulated by PKC translocation alone.
Dual mechanisms in priming of the chemoattractant-induced respiratory burst in human granulocytes. A Ca2+-dependent and a Ca2+-independent route.
Authors: Koenderman L , Yazdanbakhsh M , Roos D , Verhoeven A J 
Published: December 2022

Abstract
After interaction with so-called priming agents, the respiratory burst in human granulocytes does not become activated, but is enhanced upon subsequent stimulation with the chemoattractant FMLP. Investigating the mechanism of the priming reaction, we found that a transient rise in the cytosolic free calcium concentration [( Ca2+]i) suffices to irreversibly prime human granulocytes. Thus, platelet-activating factor (PAF) induced a transient increase in [Ca2+]i and primed the cells to an enhanced respiratory burst upon subsequent interaction with FMLP. Artificially, the transient rise in [Ca2+]i was mimicked by addition and subsequent removal of the Ca2+ ionophore ionomycin; this treatment too, primed the respiratory burst of the granulocytes. The priming induced by ionomycin was completely abolished when [Ca2+]i changes were buffered during exposure of the cells to the ionophore. The priming induced by PAF was only partially inhibited under [Ca2+]i-buffering conditions during priming, indicating that multiple pathways exist in the priming of granulocytes by PAF.
Immunosuppressive properties of electrophoretically "slow" and "fast" form alpha 2-macroglobulin. Effects on cell-mediated cytotoxicity and (allo-) antigen-induced T cell proliferation.
Authors: Petersen C M , Ejlersen E , Moestrup S K , Jensen P H , Sand O , Sottrup-Jensen L 
Published: December 2022

Abstract
Lymphokine activated killer cell lysis of K562 cells was inhibited by alpha 2-macroglobulin (alpha 2M), soybean trypsin inhibitor, and alpha 1-proteinase inhibitor. In serum free medium 2 mg/ml alpha 2M suppressed target cell lysis in a 4-h cytotoxic assay with about 40%. Suppression was dose and time dependent. Cytotoxicity was unaffected by alpha 2M concentrations less than 0.25 mg/ml, and by alpha 2M added later than 1.5 h from start of assay. Pre-treatment of effector (but not of target) cells with alpha 2M was even more suppressive than the presence of alpha 2M during assay. Cell-mediated cytotoxicity was not inhibited by alpha 2M treated with methylamine or by various alpha 2M-proteinase complexes. In contrast, alpha 2M-proteinase complex as well as native alpha 2M suppressed the proliferation of Ag-activated T cells. However, methylamine-treated alpha 2M did not inhibit T cell proliferation, and suppression by alpha 2M-proteinase complex was significantly reduced after inhibition of the alpha 2M-bound proteinase. On incubation at 4 degrees C with lymphokine-activated killer cells, alpha 2M reacted with cell associated proteinases and changed from electrophoretically "slow" to "fast" form. Cell associated proteinases bound by alpha 2M showed chymotrypsin- and trypsin-like specificities and their activity surpassed activity caused by cellular leakage and secretion. The present results strongly indicate that alpha 2M mediates immunosuppression in its capacity as a proteinase inhibitor and suggest inhibition of (T)cell surface-associated proteinases as a possible mode of suppression.
Selective up-regulation of endothelial cell class I MHC expression by cytokines from patients with lymphatic filariasis.
Authors: Freedman D O , Nutman T B , Jamal S , Kumaraswami V , Ottesen E A 
Published: December 2022

Abstract
Local host immune responses to the lymphatic-dwelling filarial parasite Wuchereria bancrofti are important in the pathogenesis of the lymphangitis that leads to filarial elephantiasis. That the lymphatic endothelial cells may be important in this inflammatory process was shown by the ability of supernatants generated from filarial Ag-driven PBMC of individuals with filarial elephantiasis caused by W. bancrofti infection to up-regulate class I MHC expression on human umbilical vein endothelial cells when compared to unstimulated control supernatants from the same individual (relative fluorescence intensity = 159% +/- 13.5; p less than 0.001). In contrast, individuals with the same filarial infection but manifesting no lymphatic disease were unable to generate, in response to filarial Ag the cytokines required for this activation (relative fluorescence intensity = 93% +/- 2.6). Supernatants induced by a non-filarial Ag (purified protein derivative) were able to effect class I MHC up-regulation in both patient groups. The same filarial Ag-driven supernatants did not cause detectable class II MHC staining on human umbilical vein endothelial cells. These results suggest a likely role for parasite Ag-driven, cytokine-mediated endothelial cell activation in the pathogenesis of lymphatic inflammatory/obstructive filarial disease.