bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demonstration that human B cells respond differently to interleukin 2 and B cell differentiation factor based on their stages of maturation.
Authors: Nakagawa T , Nakagawa N , Goldstein H , Volkman D J , Fauci A S 
Published: December 2022

Abstract
The mechanisms whereby interleukin 2 (IL 2), interferon-gamma (IFN-gamma), and B cell differentiation factor (BCDF) alone or in combination modulate human B cell differentiation are currently under intensive study. To dissect out the effects of individual lymphokines contained in mixed lymphocyte reaction-culture supernatants (MLR-CS) on B cell differentiation, we employed pure factors that possessed the same activity as factors contained in MLR-CS (IL 2: 50 U/ml, IFN-gamma: 7 U/ml, BCDF-Nal: 5 pM/ml, BCDF-YA2: 12.5% v/v) singly and in combination to human B cells. By activating purified human B cells with Staphylococcus aureus Cowan I (SAC) for 3 days, separating B blast cells by the Percoll centrifugation method, and then either using these B blast cells as B cells in the earlier stage after SAC-activation, or further culturing these B blast cells for 4 more days without any stimuli and using these B cells as B cells in the later stage after SAC-activation, we could define two different populations of cells. Disparity in the populations could be demonstrated by the observation that B cells in the earlier stage were 81.2% Tac-antigen+, 23.2% B2+, 68.9% transferrin receptor+, and 90.5% HLR-DR+, whereas B cells in the later stage were observed to be less positive for each surface antigen: 36.1% Tac-Ag+, 8.3% B2+, 45.3% transferrin receptor+, and 58.7% HLR-DR+. By adding each factor to both B cell fractions, we also demonstrated functional differences in the two populations. B cells in the earlier stage of activation only differentiated in response to IL 2 or IL 2 + IFN-gamma but not to BCDF, which was in contrast to B cells in the later stage that did not differentiate in response to IL 2 but did differentiate to BCDF. However, B cells in both stages proliferated in response to IL 2 but not to BCDF. Finally, we separated B cells in the later stage into two populations by the Percoll discontinuous gradient centrifugation. Lower density (larger) B cells were observed to proliferate but not to differentiate in response to IL 2, whereas higher density (smaller) B cells were observed to differentiate in response to BCDF. Therefore, we conclude that activated B cells initially become large and gain Tac-Ag and differentiate in response to IL 2 alone as well as the combination of IL 2 and IFN-gamma, whereas later in the more mature stage they become smaller again and differentiate into Ig-secreting cells only in response to BCDF.
Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate.
Authors: Knudsen P J , Dinarello C A , Strom T B 
Published: December 2022

Abstract
The effect of prostaglandins and cyclic 3',5'-adenosine monophosphate (cAMP) on expression of human interleukin 1 (IL 1) activity was investigated in the promonocytic tumor cell line U937 and peripheral blood monocytes. After in vitro stimulation by bacteriotoxins, monocytes express IL 1 activity, as measured by the thymocyte costimulation assay. Although high doses of bacteriotoxins impaired expression of IL 1, this effect was reversed by indomethacin. When stimulated monocytes were cultured with exogenous prostaglandins, including PGE2 and PGI2, expression of IL 1 was reversibly inhibited. Interaction of U937 cells with PGE2 resulted in a transient increase in cellular cAMP concentration during the first hour of exposure. Other agents that cause an increase in levels of cellular cAMP, including theophylline, isobutylmethylxanthine, dibutyryl cAMP, or cholera toxin, also reversibly reduced expression of IL 1 by stimulated monocytes. The effect of these agents on levels of IL 1 mRNA was analyzed. TSS-stimulated increase in levels of IL 1-encoding mRNA was studied both by DNA-RNA hybridization analysis performed with an IL 1-beta cDNA probe and by injecting U937 polyadenylated mRNA into frog oocytes and then measuring expression of IL 1 activity in the oocyte supernatant. Agents that increased levels of cellular cAMP did not alter levels of IL 1 mRNA accumulation or global protein synthesis in TSS-stimulated U937 cells. IL 1 stimulates synthesis of prostaglandins that reach high levels during immune and inflammatory reactions. Our data suggest that prostaglandins participate in an autoregulatory pathway that posttranscriptionally reduces expression of IL 1 activity.
The effects of adenosine agonists on human neutrophil function.
Authors: Schrier D J , Imre K M 
Published: December 2022

Abstract
Adenosine is a potent physiologic substance with a variety of biologic activities. Many of the effects of adenosine appear to be mediated by two populations of cell-surface adenosine receptors (A1 and A2). We have examined the effects of several adenosine receptor agonists on human neutrophils stimulated with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). The results indicate that both superoxide anion generation and degranulation (as assessed by lysozyme release) are inhibited. Inhibition correlated most strongly with A2 receptor affinity for both parameters and was reversible by the adenosine receptor antagonist 8-phenyltheophylline. Because toxic oxygen metabolites and degradative enzymes are implicated in a variety of inflammatory disorders, adenosine agonists may be useful probes to help expand our knowledge of the role of these mediators in human disease.
Two roles for Ia in antigen-specific T lymphocyte activation.
Authors: Kim K H , Shivdasani R A , Thomas D W 
Published: December 2022

Abstract
In this study we examined the mechanism by which a PPD-specific murine T cell hybridoma, 8B2, recognized PPD associated with antigen-presenting cells (APC) in a manner genetically restricted by I-Ad. It was found that PPD-pulsed APC that were glutaraldehyde-fixed and treated with anti-Ia monoclonal antibody (abbreviated as PGM) were unable to stimulate the 8B2 T cells, as expected, due to inhibition caused by antibody binding to the Ia. However, addition of non-antigen-treated, glutaraldehyde-fixed APC (abbreviated as G) to cultures containing 8B2 T cells and PGM restored T cell activation, as determined by IL 2 production. This second non-antigen-specific function provided by the additional APC, G, was attributed to Ia and could be substituted by APC plasma membranes and by soluble membrane extracts. Genetic restriction analysis in which a variety of Ia-positive and Ia-negative cell lines and B cell blasts from different mouse strains were used as PGM or as G showed that each APC provided different Ia determinants that were specifically recognized by the T cells. PGM cells had to express I-Ad in order to present the PPD determinant, whereas the non-antigen-specific function was specific for I-Ad or I-Ab. These results suggest that the anti-Ia antibody does not interfere with the PPD/I-Ad-specific determinant bound by the antigen-specific T cell receptor, but prevents a second non-antigen-specific interaction with another region of the Ia molecule, which is provided by G. These two roles for Ia (antigen-specific and non-antigen-specific) were also found for activation of normal polyclonal PPD-specific T cell responses; thus they are not unique to the 8B2 T cell, but are generally applicable. In addition, T cell interactions with PGM and with G each provide different intracellular activation signals. This was determined by substituting the PGM or the G with either the tumor promoter phorbol 12-myristate 13-acetate (PMA) or the Ca++ ionophore, ionomycin. It was found that 8B2 T cells cultured with PGM and ionomycin, but not with PGM and PMA, were activated for IL 2 production. Neither PMA nor ionomycin in conjunction with G resulted in T cell activation. Taken together, these results indicate that 8B2 T cell activation involves APC Ia antigens in two different ways: one is to contribute to the presentation of the foreign PPD antigen, and a second is a non-antigen-specific Ia-T cell interaction necessary to provide additional intracellular activation signals.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration of F(ab')2 fragments of monoclonal antibody to L3T4 inhibits humoral immunity in mice without depleting L3T4+ cells.
Authors: Gutstein N L , Wofsy D 
Published: December 2022

Abstract
Treatment of mice with monoclonal antibody (MAb) to L3T4 blocks the humoral immune response to antigens administered when L3T4+ cells are depleted. To determine whether depletion of target cells is required to suppress immunity, we examined the effect of treatment with F(ab')2 fragments of anti-L3T4 on the response of BALB/c mice to immunization with bovine serum albumin (BSA) in complete Freund's adjuvant. Treatment with F(ab')2 fragments of anti-L3T4 every 2 days (1 mg i.p.) beginning at the time of immunization significantly inhibited production of anti-BSA antibodies without depleting target cells. A single injection of anti-L3T4 fragments at the time of immunization also significantly inhibited production of anti-BSA antibodies, but was not as effective as repeated administration of the MAb fragments (75% inhibition compared with 98% inhibition; p less than 0.05). Moreover, one injection of anti-L3T4 fragments stimulated a host immune response to the rat MAb, whereas sustained therapy with the anti-L3T4 fragments blocked this response. Surprisingly, low doses (less than or equal to 10 micrograms/mouse) of intact rat MAb to L3T4 also stimulated a host immune response to the MAb but, as previously reported, higher doses of intact MAb to L3T4 did not. These findings establish that depletion of L3T4+ cells is not required to suppress immunity with MAb to L3T4. They also indicate that the ability of rat MAb to L3T4 to block the immune response to itself is dose dependent. Because the L3T4 antigen in mice is homologous to the CD4 antigen in humans, our findings have implications regarding the potential use of MAb to CD4 in humans.
The effects of polyinosinic:polycytidylic acid (pI:C) on the graft-vs-host (GVH) reaction. II. Increased NK-mediated rejection on C57BL/6 lymphocytes by (C57BL/6 X A)F1 mice.
Authors: Peres A , Nestel F P , Seemayer T A , Lapp W S 
Published: December 2022

Abstract
We previously demonstrated that treatment of (C57BL/6 X A)F1 (F1) recipient mice with polyinosinic:polycytidylic acid (pI:C) before injection with 30 X 10(6) C57BL/6 (B6) lymphocytes prevents both the immunosuppression and pathologic lesions typical of graft-vs-host (GVH) reactions. We now report the further characterization of this phenomenon. Donor spleen and lymph node cells were labeled with fluorescein in vitro and injected into pI:C-treated or untreated mice. Two days later, recipient splenocytes were analyzed for the presence of fluorescein-labeled donor cells by flow microfluorometry. Treatment of F1 mice with pI:C resulted in a sharp reduction in the recovery of labeled B6 but not A strain parental cells. Treatment with pI:C had no effect when syngeneic recipients were used, or when F1 cells were injected into A, B6, or F1 recipients. These results suggest that pI:C treatment induces rejection of B6 but not A or F1 lymphocytes by F1 hybrid mice at least as early as 2 days after donor cell transfer. As F1 cells are not rejected by either parent, rejection does not seem to be directed against classical alloantigens. These observations are compatible with the previously described model of hybrid resistance (HR) against bone marrow grafts. The rapidity of rejection strongly suggested that natural cytotoxic mechanisms were involved, thus, natural killer (NK) cell and macrophage (M phi) cytotoxic activities were tested throughout the time when the parental cell graft was being rejected. Over this period, pI:C treatment increased cytotoxic activity against the NK-sensitive target cell line YAC-1 but had no effect on spontaneous M phi tumoricidal activity against the L5178Y and MDAY-D2 cell lines. The results suggest that NK cells, but not M phi, may be involved in the elimination of B6 parental cells by the pI:C-treated F1 mice. NK cells have been demonstrated to be radioresistant; thus, as a test of our hypothesis, we examined the effects of irradiation on the capacity of pI:C treated F1 mice to reject B6 lymphocytes. The results show that this capacity was not blocked by 750 cGy, a dose of radiation that abrogates most T and B cell functions. Furthermore, rejection of parental cells could be prevented by treatment of recipient F1 mice with antibodies to asialo GM1, a treatment that suppresses NK activity. These data demonstrate that pI:C-mediated protection from GVH-induced changes is due to increased rejection of grafted B6 parental cells by F1 NK cells, a phenomenon very similar, if not identical, to HR to bone marrow grafts.
Interaction between myelin basic protein-sensitized T lymphocytes and murine cerebral vascular endothelial cells.
Authors: McCarron R M , Spatz M , Kempski O , Hogan R N , Muehl L , McFarlin D E 
Published: December 2022

Abstract
Lymph node cells from SJL mice immunized with guinea pig myelin basic protein proliferate in vitro to the same antigen. This proliferative response is abolished by depletion of macrophages-monocytes, but can be reconstituted by the addition of cerebral vascular endothelial cells (EC) freshly isolated from syngeneic mice with adoptively transferred acute experimental allergic encephalomyelitis (EAE). Reconstitution by EC from mice with EAE can be blocked by pretreatment of EC with syngeneic anti-I-A antisera. Freshly isolated EC from normal syngeneic mice do not restore responsiveness, but can be induced to present antigen by culture with murine recombinant immune interferon-gamma or supernatants from a variety of immune cell cultures. These findings are consistent with the hypothesis that immune cells release interferon and/or other soluble factors which induce I-A molecules on EC, which subsequently acquire the capacity to present antigen. The implications of these findings relate to the migration of cells across the blood-brain-barrier into the central nervous system, and are of importance in the understanding of the pathogenesis of several neurologic disorders.
Prazosin treatment during the effector stage of disease suppresses experimental autoimmune encephalomyelitis in the Lewis rat.
Authors: Brosnan C F , Sacks H J , Goldschmidt R C , Goldmuntz E A , Norton W T 
Published: December 2022

Abstract
As part of a study on the role of vasoactive amines in experimental autoimmune encephalomyelitis (EAE), we have found that treatment beginning 7 days post-inoculation (dpi) with the specific alpha 1-adrenoceptor antagonist prazosin can significantly suppress clinical signs of disease in the Lewis rat. In this paper we have addressed the effect of treatment with prazosin commencing at varying times in the disease process. The results show that treatment during the early inductive stage (1 to 6 dpi) has no effect on the clinical course of the disease, whereas treatment commencing at the time of onset of early clinical signs (10 to 16 dpi) still significantly suppresses EAE. Leakage of serum proteins into the central nervous system (CNS) and histologic expression of EAE are also suppressed. Prazosin had no effect on lymphocyte responses to mitogen or antigen as determined by lymphocyte transformation tests when lymphocytes were exposed to prazosin in vitro, and the responses of lymphocytes from prazosin-treated animals were similar to those from saline-treated animals. These results support the hypothesis that prazosin suppresses EAE through a direct vascular effect although they do not preclude an immunologic component to its mechanism of action.
Patients with Wiskott-Aldrich syndrome have normal IgG2 levels.
Authors: Nahm M H , Blaese R M , Crain M J , Briles D E 
Published: December 2022

Abstract
The Wiskott-Aldrich Syndrome (WAS) in humans has a number of similarities to the immunodeficiencies found in CBA/N mice, including X-chromosome-linked inheritance, inability to produce antibodies to various carbohydrate antigens, susceptibility to various bacterial infections, and an imbalance in B lymphocyte subpopulations. Moreover, in both man and mice, IgG antibodies to polysaccharides are predominantly, but not exclusively, restricted to a single IgG subclass--IgG2 in man, and IgG3 in the mouse. Because CBA/N mice have a deficiency of IgG3 antibodies and because human IgG2 subclass deficiencies have been generally associated with inability to produce antibodies to carbohydrate antigens, it would seem likely that patients with WAS would have greatly reduced levels of IgG2. Quite to the contrary, the data presented here demonstrate that WAS patients have normal levels of the different IgG subclasses, including IgG2. Thus, inability to produce antibodies to carbohydrates is not always associated with IgG2 subclass deficiency.
Expression of specific binding sites on Candida with functional and antigenic characteristics of human complement receptors.
Authors: Edwards J E , Gaither T A , O'Shea J J , Rotrosen D , Lawley T J , Wright S A , Frank M M , Green I 
Published: December 2022

Abstract
Receptors for C3 degradation fragments (CR1, CR2, and CR3) are present on many human cells including phagocytes and lymphoid cells and may be critical in the attachment of invading microorganisms. In these studies Candida were found to mimic the human CR by binding erythrocytes coated with specific human C3 fragments. Yeast forms of Candida species were adhered to glass slides and were allowed to germinate. Sheep erythrocytes (E) were coated with IgM (EA) and human complement components to prepare EA, EAC14, EAC3b, EAC3bi, and EAC3d. These test cells were then examined for adherence to the organism. Antibodies to human CR1, CR2, and CR3 were used to evaluate their potential for blocking adherence of the test erythrocytes to Candida. Fluorescein-labeled antibodies to human complement receptors were also used to characterize the binding sites. EAC3bi and EAC3d, but not E, EA, or EAC14, bound extensively to the germ tubes and pseudohyphae of Candida albicans and C. stellatoidea. EAC3b bound infrequently. Other Candida species, generally considered less pathogenic, bound significantly fewer specific test erythrocytes than C. albicans. Monoclonal antibodies to human CR1 and CR3 (3D9, 1B4, C511, 2B6, anti-B2, Mo1, and anti-Mac-1), in general, did not block adherence of test erythrocytes. Blocking of adherence of EAC3bi and EAC3d test erythrocytes coated with small quantities of C3 fragments occurred with high concentrations of monoclonal (anti-CR2) HB-5 and polyclonal (anti-CR2) anti-GP 140. Immunofluorescence studies demonstrated binding of Mo-1 to the germinated forms of the organism, whereas binding of the other antibodies was not seen. These studies suggest a surface constituent on the organism similar to CR on human cells. Additional studies are necessary to further define the molecular nature of the binding site. The ability of organisms to mimic human CR may be more generalized than previously known and may serve as a mechanism for modification of the inflammatory and immune response.
Biosynthetic human GM-CSF modulates the number and affinity of neutrophil f-Met-Leu-Phe receptors.
Authors: Weisbart R H , Golde D W , Gasson J C 
Published: December 2022

Abstract
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) modulates the function of mature neutrophils by priming for enhanced chemotaxis and oxidative metabolism in response to N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). Our studies establish a relationship between f-Met-Leu-Phe receptor number and affinity and neutrophil chemotaxis and oxidative metabolism. A brief (5- to 15-min) exposure to physiologic concentrations of GM-CSF (10 pM to 100 pM) enhances f-Met-Leu-Phe-induced neutrophil chemotaxis by 85%, correlating with a rapid threefold increase (46,000/cell to 150,000/cell) in high-affinity neutrophil f-Met-Leu-Phe receptors. More prolonged incubation (1 to 2 hr) of neutrophils with GM-CSF is accompanied by a change to low-affinity f-Met-Leu-Phe receptors (Kd = 29 nM to Kd = 99 nM) concomitant with priming for enhanced neutrophil oxidative metabolism. Moreover, enhanced chemotactic responses to f-Met-Leu-Phe are no longer evident after more prolonged incubation of neutrophils with GM-CSF. These results show that a single lymphokine (GM-CSF) induces sequential changes in neutrophil f-Met-Leu-Phe receptor number and affinity that may enhance different physiologic responses.
Passive transfer of Leishmania lipopolysaccharide confers parasite survival in macrophages.
Authors: Handman E , Schnur L F , Spithill T W , Mitchell G F 
Published: December 2022

Abstract
Infection of macrophages by the intracellular protozoan parasite Leishmania involves specific attachment to the host membrane, followed by phagocytosis and intracellular survival and growth. Two parasite molecules have been implicated in the attachment event: Leishmania lipopolysaccharide (L-LPS) and a glycoprotein (gp63). This study was designed to clarify the role of L-LPS in infection and the stage in the process of infection at which it operates. We have recently identified a Leishmania major strain (LRC-L119) which lacks the L-LPS molecule and is not infective for hamsters or mice. This parasite was isolated from a gerbil in Kenya and was identified phenotypically as L. major by isoenzyme and fatty acid analysis. In this study we have confirmed at the genotype level that LRC-L119 is L. major by analyzing and comparing the organization of cloned DNA sequences in the genome of different strains of L. major. Here we show that LRC-L119 promastigotes are phagocytosed rapidly by macrophages in vitro, but in contrast to virulent strains of L. major, they are then killed over a period of 18 hr. In addition, we show that transfer of purified L-LPS from a virulent clone of L. major (V121) into LRC-L119 promastigotes confers on them the ability to survive in macrophages in vitro.
The primary structure of HLA-A32 suggests a region involved in formation of the Bw4/Bw6 epitopes.
Authors: Wan A M , Ennis P , Parham P , Holmes N 
Published: December 2022

Abstract
All HLA-B locus molecules have either the Bw4 or Bw6 epitopes. In addition, the Bw4 epitope is found on HLA-Aw23, Aw24, and A32, and Bw6 is also found on HLA-Cw3. The structural basis for these determinants and the evolution of their distribution among products of the HLA-B locus has been a long standing puzzle. To identify residues that may be involved in these determinants, we have cloned a gene for A32 and sequenced the protein encoding exons. Comparison of the predicted protein sequence with other HLA-A,B,C sequences identified residues 79 through 83 of the alpha 1 domain as having a pattern of polymorphic substitution that correlates with the presence and absence of the Bw4 and Bw6 epitopes.