bluuebunny/crossref_metadata_2025_split huggingface dataset:
High yield enzymatic conversion of intravascular leukotriene A4 in blood-free perfused lungs.
Authors: Grimminger F , Becker G , Seeger W 
Published: December 2022

Abstract
Experiments to investigate the fate of intravascularly administered leukotriene (LT) A4, an unstable intermediate of LT generation, were performed in isolated, ventilated, and blood-free perfused rabbit lungs. LT extracted from the lung effluent were separated by different reverse phase and straight phase HPLC procedures as methylated and nonmethylated compounds. Identity of eluting LT was confirmed by UV spectrum analysis and immunoreactivity. Pulmonary artery injection of 75 to 300 nmol of LTA4 resulted in the rapid appearance of cysteinyl-LT as well as LTB4 in the recirculating perfusate. The yield of these enzymatically generated LTA4 metabolites vs non-enzymatic hydrolysis products (6-trans-LTB4, 5-trans-epi-LTB4, 5,6-dihydroxyeicosatetraenoic acids) ranged above 90%. Experiments with application of tritiated LTA4 showed exclusive origin of the detected LT from the exogenously applied precursor. The time course of cysteinyl-LT appearance in the perfusate suggested metabolism of LTC4 via LTD4 to LTE4, whereas there was no evidence for LTB4 omega-oxidation. In the dose range of LTA4 used, the enzymatic conversion of this LT precursor did not approach saturation. Collectively, these data indicate that the intact pulmonary vasculature contains a hitherto not described capacity for enzymatic conversion of intravascularly offered LTA4 to both cysteinyl-LT and LTB4. This may be of biological significance for a putative transcellular biosynthesis of LT in the pulmonary microcirculation upon contact with LTA4 feeder cells, such as activated granulocytes.
Early influx of Listeria-reactive T lymphocytes in liver of mice genetically resistant to listeriosis.
Authors: Goossens P L , Marchal G , Milon G 
Published: December 2022

Abstract
Murine listeriosis is a classical model for investigating mechanisms of cellular immunity, which involves interaction of macrophages and T lymphocytes. The early course of this experimental infection is under control of a limited number of genes in the murine host. In the present study, we asked whether the early efficient control of bacterial growth in the liver of resistant mice is related to the expression of a more rapid specific immune response in this organ than in susceptible mice. Therefore, we compared the frequencies of Listeria monocytogenes-reactive T cells in blood, spleen, and liver of resistant C57BL/6 and susceptible C3H/He Past mice after i.v. injection of a high dose of Listeria (9 x 10(5) CFU). T cells were titrated through their ability to locally transfer a delayed-type hypersensitivity reaction to viable L. monocytogenes, an effector function potentially relevant to the early step of protective mechanisms. We observed (1) a 9- and 4-fold increase by day 1 in the frequency of Listeria-reactive transfer units in the blood of C57BL/6 and C3H mice, respectively, (2) no increase in the number of Listeria-reactive transfer units in the spleen of 2-day infected mice of both strains, and (3) a 90-fold increase, at day 2, in the number of Listeria-reactive transfer units in the liver of resistant C57BL/6 compared with only a 9-fold increase in the liver of susceptible C3H/He. These results suggest that the ability of C57BL/6 mice to control the early bacterial growth (0 to 48 h) in their liver, may be related to a rapid influx of L. monocytogenes-reactive T lymphocytes.
Differential recognition of Leishmania aethiopica antigens by lymphocytes from patients with local and diffuse cutaneous leishmaniasis. Evidence for antigen-induced immune suppression.
Authors: Akuffo H O , Fehniger T E , Britton S 
Published: December 2022

Abstract
Data are presented to suggest that differential Ag expression by parasites derived from diffuse (DCL) vs local (LCL) cutaneous leishmaniasis patients may be responsible for the Ag-specific anergy seen in DCL patients. The evidence suggests that promastigotes derived from DCL patients express epitopes which preferentially stimulate suppressor activities in DCL patients. These determinants appear to be expressed less, if at all by promastigotes derived from LCL patients. The Ag-specific suppression or nonresponsiveness which dominates the immune response in DCL patients during an active infection can be abrogated by drug treatment or removal of live DCL parasites, which suggests that Ag-induced regulatory cells, probably of T cell lineage, are most likely responsible for the nonresponsiveness seen in untreated DCL patients. Thus the mechanisms of immune regulation operating in this disease differ from that of lepromatous leprosy where the specific unresponsiveness (anergy) is irreversible even after successful treatment.
A study of functionally active amino acids involved in the interaction of HLA-A2 or HLA-A3 molecules with cytolytic T lymphocytes.
Authors: Healy F , Sire J , Gomard E , Yssel H , Jordan B , Levy J P 
Published: December 2022

Abstract
A large series of HLA-A2/HLA-A3 recombinant genes were generated by using the in vivo recombination technique. These genes have each been modified in the last two-thirds of the third exon such that one or several HLA-A2-specific substitutions have been made in the HLA-A3 gene and vice versa. The recombinant genes were transfected into the murine cell line P815 and the transfectants were used as targets for a series of 20 human CTL lines or clones specific for HLA-A2 or HLA-A3, or restricted by HLA-A2 and specific for influenza A. Several patterns of anti-HLA-A2, anti-HLA-A3, and HLA-A2-restricted anti-influenza CTL activity were observed and when uncloned cell lines were studied, a progressive selection of some clones with a similar pattern of activity was regularly found. From the comparison of these different patterns the following conclusions can be drawn: 1) In most but not all cases both domains of the class I molecule were essential for CTL recognition, but residue 152 was critically important for the majority of CTL tested; 2) amino acids 114/116 were also critical in most cases, and their position close to amino acid 152 in the tertiary structure of the molecule may have some functional significance; and 3) amino acid 161, although highly conserved, plays an unexpected but very important role in CTL function.
Identification by site-directed mutagenesis of amino acid residues contributing to serologic and CTL-defined epitope differences between HLA-A2.1 and HLA-A2.3.
Authors: Hogan K T , Clayberger C , Bernhard E J , Walk S F , Ridge J P , Parham P , Krensky A M , Engelhard V H 
Published: December 2022

Abstract
Site-directed mutagenesis of HLA-A2.1 has been used to identify the amino acid substitutions in HLA-A2.3 that are responsible for the lack of recognition of the latter molecule by the HLA-A2/A28 specific antibody, CR11-351, and by HLA-A2.1 specific CTL. Three genes were constructed that encoded HLA-A2 derivatives containing one of the amino acids known to occur in HLA-A2.3: Thr for Ala149, Glu for Val152, and Trp for Leu156. Three additional genes were constructed that encoded the different possible combinations of two amino acid substitutions at these residues. Finally, a gene encoding all three substitutions and equivalent to HLA-A2.3 was constructed. These genes were transfected into the class I negative, human cell line Hmy2.C1R. Analysis of this panel of cells revealed that recognition by the antibody CR11-351 was completely lost when Thr was substituted for Ala149, whereas substitutions at amino acids 152 and 156, either singly or in combination, had no effect on the binding of this antibody. The epitopes recognized by the allogeneic and xenogeneic HLA-A2.1 specific CTL clones used in this study were all affected by either one or two amino acid substitutions. Of those epitopes sensitive to single amino acid changes, none were affected by the substitution of Thr for Ala149, whereas all of them were affected by at least one of the substitutions of Glu for Val 152 or Trp for Leu156. Overall, amino acid residue 152 exerted a stronger effect on the epitopes recognized by HLA-A2.1 specific CTL than did residue 156. Of those epitopes affected only by multiple amino acid substitutions, double substitutions at residues 149 and 152 or at 152 and 156 resulted in a loss of recognition, whereas a mutant with substitutions at residues 149 and 156 was recognized normally. This reemphasizes the importance of residue 152 and indicates that residue 149 can affect epitope formation in conjunction with another amino acid substitution. These results are discussed in the context of current models for the recognition of alloantigens and in light of the recently published three-dimensional structure of the HLA-A2.1 molecule.
Constitutive expression of a phosphorylated activation antigen (Leu 23) by CD3bright human thymocytes.
Authors: Testi R , Phillips J H , Lanier L L 
Published: December 2022

Abstract
Leu 23 is a human cell surface differentiation Ag expressed very early during lymphoid cell activation. Resting T lymphocytes do not express Leu 23. However, expression of Leu 23 glycoprotein can be induced on the Jurkat T leukemia cell line within a few hours after stimulation with soluble anti-CD3 mAb or Con A. After removal of the stimulus Leu 23 is expressed for greater than 30 h. A total of 20 to 30% of resting human thymocytes was unexpectedly stained by anti-Leu 23 mAb. Biochemical analysis revealed that the Leu 23 Ag expressed on thymocytes is a phosphorylated disulfide-linked dimer composed of 28- and 32-kDa subunits. Within the thymus, Leu 23 is preferentially expressed on the CD3bright, mostly CD4+ CD8- or CD4- CD8+ subpopulations. By contrast, CD3dim CD4+CD8+ thymocytes expressed only very low levels of Leu 23, and CD7+ CD3- CD4- CD8- thymocytes were Leu 23-. However, Leu 23 was induced on the CD3dim thymocytes by in vitro culture of thymocytes with anti-CD3-conjugated Sepharose. The transition from CD3dim to CD3bright within the thymus may be an important differentiation stage and influence selection of the antigenic repertoire. Therefore, the ability to detect subpopulations within the thymus that express Leu 23 Ag may help to identify thymocytes activated in vivo, possibly by the functional engagement of their CD3/TCR.
Inverse relationship between proliferation and differentiation in a human TNP-specific B cell line. Cell cycle dependence of antibody secretion.
Authors: Golding B , Pillemer S R , Roussou P , Peters E A , Tsokos G C , Ballow J E , Hoffman T 
Published: December 2022

Abstract
Studies of an EBV-transformed and TNP-specific human B cell line revealed that, unlike myeloma or hybridoma cell lines that consist mainly of fully differentiated cells, most of the cloned EBV-transformed cells were not fully differentiated, as judged by inability to bind TNP-SRBC and to secrete anti-TNP antibody. The minority of more differentiated cells were selected by TNP-SRBC rosetting. They were found to proliferate to a lesser extent than nonrosetting cells and to contain increased numbers of antibody-secreting cells. This inverse relationship between proliferation and differentiation was also shown to be cell cycle related in that the TNP-SRBC rosetting cells resided, to a greater extent than the nonrosetting cells, in the G1 phase of the cell cycle. The finding that the G1 phase of the cell cycle was associated with differentiation into anti-TNP secreting cells was confirmed by demonstrating that treatment with hydroxyurea, which arrests the cells in G1, resulted in decreased proliferation and an increased proportion of antibody-secreting cells. Similarly, addition of phorbol ester resulted in increased antibody secretion and decreased proliferation, suggesting a role for protein kinase C in this differentiation pathway. The strategy of increasing the number of antibody-producing cells in this human EBV line, by promoting differentiation of the cells in G1, may be relevant to the large scale production of specific human mAb for the treatment and diagnosis of human diseases.
Individual class II-restricted antigenic determinants of the same protein exhibit distinct kinetics of appearance and persistence on antigen-presenting cells.
Authors: Eisenlohr L C , Gerhard W , Hackett C J 
Published: December 2022

Abstract
The kinetics of presentation of class II-restricted T cell determinants of influenza virus hemagglutinin (HA) was investigated over a 48-h time course after pulsing of A20 B lymphoma APC with non-replicative virus or isolated HA. At intervals after Ag pulse, APC were fixed with paraformaldehyde to arrest Ag processing and to preserve the expression levels of the presented determinants. Expression of T cell sites at each time point was probed by a panel of BALC/c T hybridomas specific for the HA of influenza A/Puerto Rico/8/34 virus, recognizing either site 1 (residues 111 to 119), site 2 (126 to 138), or site 3 (302 to 313). Characteristic patterns of presentation were observed for each site: sites 2 and 3 achieved maximal expression by 8 h post pulse, but declined thereafter, whereas site 1 presentation continued to increase over time. The quantitative expression of each T cell site was affected by the proteolysis inhibitor leupeptin, resulting in partial inhibition of site 1, complete blocking of site 2, but enhancement of site 3. However, the expression kinetics of sites 1 and 3, which could be observed in the presence of the inhibitor, remained qualitatively unchanged. These observations indicate that some T cell determinants (e.g., HA site 1) may exhibit a greater longevity of expression on APC than other antigenic sites of the same protein. Differences in the persistence of surface expression of distinct T cell sites may be a factor in their relative immunodominance.
Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition.
Authors: Symons J A , Wood N C , Di Giovine F S , Duff G W 
Published: December 2022

Abstract
An ELISA was used to measure soluble IL-2R (sIL-2R) in the sera and synovial fluids of patients with rheumatic diseases. Patients with rheumatoid arthritis had raised levels of sIL-2R both in their sera and in their synovial fluid compared to patients with osteoarthritis and age-matched healthy controls. Mononuclear cells from the synovial fluid of rheumatoid arthritis patients were found to produce spontaneously high levels of sIL-2R which eluted at approximately m.w. 40,000 on gel filtration. In contrast, autologous peripheral blood cells only produced comparable levels upon stimulation with mitogenic lectin. Sequential studies indicated that serum sIL-2R levels were highly correlated with disease activity, indicating that measurement of sIL-2R may be a useful clinical marker in the future. Within the joint, synovial fluid sIL-2R levels correlated significantly with immunoreactive IL-1 beta levels, providing evidence for a role of IL-1 in immune activation in the synovium. In synovial fluids, sIL-2R level also correlated with functional inhibition of IL-2-driven responses in vitro. Furthermore, sIL-2R immunoreactivity in synovial fluid eluted at m.w. 100,000 coeluting with IL-2-inhibitory activity and consistent with a role for sIL-2R in down-regulation of IL-2 responses. The abnormal m.w. may be accounted for by complex formation in the synovial fluid. Given the ability of sIL-2R to bind IL-2, the presence of sIL-2R within the joint may contribute to the well documented "IL-2 defect" seen in rheumatoid arthritis.
Anti-proliferative effect of IFN-gamma in immune regulation. II. IFN-gamma inhibits the proliferation of murine bone marrow cells stimulated with IL-3, IL-4, or granulocyte-macrophage colony-stimulating factor.
Authors: Gajewski T F , Goldwasser E , Fitch F W 
Published: December 2022

Abstract
A biphasic dose response curve was observed when the bone marrow-derived cell line FDCP1, used as an indicator line for IL-3 bioassays, was exposed to supernatants from some activated T cell clones but not others. The active component which inhibited proliferation at the higher supernatant concentrations appeared to be IFN-gamma, based on the following observations. 1) Only those culture supernatants which contained IFN-gamma gave a biphasic dose response curve; 2) with these supernatants, an anti-IFN-gamma mAb augmented the proliferation of FDCP1 cells at the higher supernatant concentrations; and 3) rIFN-gamma profoundly inhibited the proliferation of FDCP1 cells stimulated with rIL-3 or rIL-4. rTNF-alpha inhibited FDCP1 proliferation only to a modest extent, yet the combination of rTNF-alpha + rIFN-gamma provided greater inhibition than each agent alone. The proliferation of a second bone marrow-derived cell line, DA1, was not inhibited by rIFN-gamma or rIFN-gamma + rTNF-alpha when stimulated with rIL-3 or recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Fresh bone marrow cells also showed a suboptimal proliferative response when stimulated with T cell supernatants containing IFN-gamma, and this response was augmented considerably upon the addition of anti-IFN-gamma mAb. Bone marrow cell proliferation was observed upon exposure to rIL-3, rIL-4, or rGM-CSF, and these responses were inhibited by rIFN-gamma; rTNF-alpha also produced a synergistic effect with these cells. Bone marrow cell colony formation stimulated by rIL-3 or rGM-CSF also was inhibited by rIFN-gamma. Colony formation in bone marrow cell cultures was not observed in response to rIL-4. Collectively, these results suggest that Th1 cells, which in addition to IL-3 and GM-CSF also produce IFN-gamma, may regulate hemopoietic cell proliferation and colony formation differently from the way Th2 cells do, which do not produce IFN-gamma.
Characterization of the murine T cell receptor for IgE (Fc epsilon RII). Demonstration of shared and unshared epitopes with the B cell Fc epsilon RII.
Authors: Mathur A , Conrad D H , Lynch R G 
Published: December 2022

Abstract
Antigenic relationships between the low affinity Fc epsilon R present on murine B and T lymphocytes were studied. A rat mAb (B3B4) and two polyclonal antisera produced by immunizing with the murine B lymphocyte Fc epsilon RII were examined for their ability to inhibit binding of IgE to murine B or T lymphocytes, using an IgE-specific rosette assay. One polyclonal antiserum (goat-anti-mouse Fc epsilon R) inhibited binding of IgE to both B and T lymphocytes, whereas another polyclonal antiserum (rabbit-anti-mouse Fc epsilon R) and the rat mAb inhibited the binding of IgE to B lymphocytes but did not influence the binding of IgE to T lymphocytes. When lymphocytes were surface labeled with 125I, 49-kDa and 38-kDa IgE-binding proteins were immunoprecipitated from B lymphocyte lysates by B3B4 and from B and T lymphocyte lysates by the goat antiserum. Taken together, these results suggest that the Fc epsilon R present on murine B and T lymphocytes are structurally related receptors that share some, but not all, epitopes.
Structural polymorphism of the human platelet Fc gamma receptor.
Authors: Looney R J , Anderson C L , Ryan D H , Rosenfeld S I 
Published: December 2022

Abstract
A variable T lymphocyte proliferative response to murine IgG1 anti-T3 monoclonal antibodies, in which most North American Caucasians respond whereas a minority do not, is well established. This is most likely the result of a genetic polymorphism manifested by 1) the inability of the monocyte 40-kDa IgG FcR of some individuals to bind murine IgG1, and 2) a distinctive trimorphic pattern on IEF of the monocyte 40-kDa FcR, one form being seen in all individuals who do not respond and another form (or a combination of both forms) being seen in those who do respond. We have evaluated the IEF patterns of the platelet 40-kDa FcR and find that in every individual tested the pattern for platelet FcR correlates with that seen for the monocyte 40-kDa FcR pattern. Furthermore, the platelets of those individuals whose "nonresponder" monocyte 40-kDa FcR did not mediate a murine IgG1 anti-T3 response did not respond with an aggregation reaction to murine IgG1 immune complexes (opsonized E). In contrast, platelets from donors possessing "responder" monocytes displayed positive "aggregation" responses to E coated with murine IgG1 antibody. However, the platelet FcR structural polymorphism described earlier did not correlate with the donor-specific variability in capacity of platelets to respond functionally to aggregated human IgG described in an earlier paper. Rather, the variation in capacity of platelets from individual donors to respond functionally to aggregated human IgG was related to the quantitative expression of platelet FcR. These data indicate that the molecular mechanisms responsible for the platelet 40-kDa FcR structural polymorphism are quite different from the mechanisms governing the variation in quantitative expression of the receptor.
Substance P augmentation of CSF-1-stimulated in vitro myelopoiesis. A two-signal progenitor restricted, tuftsin-like effect.
Authors: Moore R N , Osmand A P , Dunn J A , Joshi J G , Rouse B T 
Published: December 2022

Abstract
The inflammatory neuropeptide substance P acted as a costimulant for macrophage CSF-1-induced clonal proliferation of murine marrow-derived two signal-dependent mononuclear phagocyte progenitors. Substance P had no effect on clonal proliferation by progenitors responding solely to CSF-1. Substance P fragment 2-11 had no costimulatory activity; however, SP fragment 1-4 retained the full activity of the parent undecapeptide. Fragment 1-4 (ARG-PRO-LYS-PRO), a peptide containing a PRO residue between two positive charges, is a tuftsin-like (THR-LYS-PRO-ARG) tetrapeptide, and tuftsin exerted an identical costimulatory effect. Substance P, SP:1-4, and tuftsin were optimally effective as costimulants at 10(-7) to 10(-6) M. (ALA1)-tuftsin, an inhibitory analog of tuftsin, was a potent negative regulator of two signal-dependent colony formation. (ALA1)-tuftsin at concentrations less than or equal to 10(-9) M exerted dose-dependent inhibition of the positive effects of optimal concentrations of all of the co-stimulants tested, including bacterial LPS. The inhibitory tetrapeptide was equivalent in activity to ferritin, an established inhibitor of two signal-dependent colony formation. The results indicated that SP may influence myelopoiesis in addition to its other inflammatory and immunopotentiating properties. In addition, a potentially valuable modulator of SP and LPS responses in this system, (ALA1)-tuftsin, was identified.