bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the induction of tolerance to alloantigens. II. The generation of serum factor(s) able to transfer alloantigen-specific tolerance for delayed-type hypersensitivity by portal venous inoculation with allogeneic cells.
Authors: Fujiwara H , Qian J H , Satoh S , Kokudo S , Ikegami R , Hamaoka T 
Published: December 2022

Abstract
The administration of C3H/He spleen cells into allogeneic BALB/c mice via portal venous (p.v.) route resulted in C3H/He alloantigen-specific tolerance for delayed-type hypersensitivity (DTH) responses. When serum from these tolerant BALB/c mice were transferred into naive syngeneic BALB/c mice, the recipient mice lost the capability of generating DTH responses as induced by s.c. immunization with C3H/He cells. Tolerance was transferred only by serum from BALB/c mice inoculated p.v. with C3H/He cells, but not by serum from C3H/He mice inoculated p.v. with C3H/He cells, or BALB/c mice inoculated i.v. with C3H/He cells. This tolerogenic activity in serum from p.v. inoculated BALB/c mice was C3H/He alloantigen specific, because the transfer of the serum did not interfere with the development of anti-C57BL/6 DTH responses in recipient BALB/c mice. Such a serum factor(s) was inducible as early as 1 wk after the inoculation of C3H/He cells into BALB/c mice and not associated with anti-C3H/He alloantibody activity. Moreover, anti-C3H/He or C57BL/6-specific tolerogenic factor(s) prepared in the respective BALB/c or C3H/He mice was successfully transferred into totally allogeneic recipient mice, indicating no requirement of H-2, as well as non-H-2 restriction for the function of serum tolerogenic factor(s). Thus this study demonstrates that p.v. inoculation of allogeneic cells generates serum factor(s) able to transfer in H-2 and non-H-2-unrestricted manners the in vivo tolerance of the alloreactivity specific for alloantigens used for p.v. inoculation.
Thy-1+ epidermal cells proliferate in response to concanavalin A and interleukin 2.
Authors: Nixon-Fulton J L , Bergstresser P R , Tigelaar R E 
Published: December 2022

Abstract
Mouse epidermal cells (EC) are composed of at least two phenotypically discrete populations of cells that in epidermal sheets have a dendritic morphology: Ia+ Langerhans cells (LC) and dendritic, bone marrow-derived, Ia- cells that express Thy-1 antigen (Thy-1+ dEC). Thy-1+ dEC lack other typical T cell markers such as L3T4, Lyt-1, and Lyt-2; however they do express Ly-5 and asialo GM1 in common with NK cells and certain other leukocytes. To investigate the functional capabilities of Thy-1+ dEC in vitro, cell suspensions prepared from trypsin-disaggregated sheets of mouse body wall epidermis were first enriched to 8 to 20% Ia+ and 20 to 40% Thy-1+ cells by centrifugation over Isolymph and then were cultured for 2 to 10 days with Concanavalin A (Con A) and/or partially purified rat IL 2. Con A-induced proliferation of EC was readily seen, with the maximal response occurring at a Con A concentration of 2.5 micrograms/ml on day 5 of culture. Con A responses were significantly enhanced by the continuous presence of 1 microgram/ml indomethacin. Responses both in the presence and absence of Con A were significantly enhanced by the addition of 5 to 10 U/ml of partially purified rat IL 2; proliferation in cultures stimulated by both Con A and IL 2 continued to increase throughout the 10-day culture period. Culture of fluorescence-activated cell sorter (FACS)-separated EC suspensions revealed that Thy-1-depleted EC and irradiated Thy-1+ EC failed to proliferate in response to Con A and IL 2, whereas unirradiated purified Thy-1+ EC gave enhanced Con A- and IL 2-induced responses compared with the unseparated population. Finally, to distinguish between the proliferation of small numbers of mature peripheral T cells and that of Thy-1+ dEC, antibody and complement-depletion studies were conducted with an unusual monoclonal anti-Thy-1 reagent, 20-10-5S, and with the anti-T cell reagents, anti-L3T4 and anti-Lyt-2. Thy-1+ dEC, but not LC, express the 20-10-5S determinant; furthermore, in CBA (Thy-1.2) mice 20-10-5S reacts with Thy-1+ dEC, thymocytes, and peripheral T cells, whereas in AKR/J (Thy-1.1) mice, it reacts only with Thy-1+ dEC and thymocytes and not with peripheral T cells. Pretreatment of AKR/J EC with 20-10-5S and complement abolished the capacity of such cells to respond to Con A and to IL 2.(ABSTRACT TRUNCATED AT 400 WORDS)
Ocular immune responses. II. Priming of A/J mice in the vitreous induces either enhancement of or suppression of subsequent hapten-specific DTH responses.
Authors: Foster C S , Monroe J G , Campbell R , Kalpaxis J , Wetzig R , Greene M I 
Published: December 2022

Abstract
We previously showed that the "immunologic privilege" of the anterior chamber results not from afferent blockade, but rather from induction of hapten-specific suppressor T cells that appear after anterior chamber priming with antigen. These suppressor T cells induced by anterior chamber priming differ from those induced by i.v. priming in their ability to block the efferent as well as the afferent limb of the immune response and in their lack of idiotypic surface receptors detected by rabbit anti-idiotypic antibody. We now report that intravitreal priming with haptenated syngeneic spleen cells does not result in generation of suppressor cells, but rather, can in some instances result in an enhanced systemic immunoreactivity to the priming hapten. If soluble antigenic preparations are used, however, intravitreal priming results in the generation of the suppressor T cells, which suppress subsequent DTH and CTL responses to the immunizing hapten. The suppressor cell generation after intravitreal priming is a cyclophosphamide-sensitive process. These results demonstrate that soluble products are processed differently in ocular compartments compared with cell surface coupled ligands, and further demonstrate that the generation of hapten-specific suppressor T cells is dependent, at least in part, on the form and on the specific compartment of the eye that is inoculated.
Mitogen-stimulated phospholipid synthesis in normal and immune-deficient human B cells.
Authors: Chien M M , Yokoyama W M , Ashman R F 
Published: December 2022

Abstract
Eight patients with common variable panhypogammaglobulinemia were shown in the in vitro Ig biosynthesis assay to have defective B cell responses to pokeweed mitogen (PWM). Phospholipid synthesis was assessed in the B cell plus monocyte fraction (MB) and irradiated T cells (T*) of patients and paired normal controls. Cell populations were studied separately and in the four possible combinations (1:1), with and without PWM, to reveal the effect of cell interactions. At 16 to 20 hr the mean stimulation index (SI) +/- standard error for MB cells alone was 1.01 +/- 0.02 for eight patients and 0.99 +/- 0.02 for the paired normals; the T* cell SI was 1.25 +/- 0.04 for patients and 1.28 +/- 0.05 for normals. Combinations of normal MB cells with normal T* cells showed significantly higher SI when compared with the combinations of normal MB cells with patient T* cells (p less than 0.005). However, the combination of patient MB cells with patient T* cells and the combination of patient MB cells with normal T* cells were not significantly different in SI (0.05 less than p less than 0.1). Isolation of patient and normal B cells, T* cells, and monocytes after the choline pulse showed that patient B cells gave a higher SI with normal T* help than with patient T* help. Of greatest interest is the finding that patient B cells that were defective in PWM-stimulated Ig production nevertheless showed a phospholipid synthesis response to PWM in the normal range, suggesting that the maturation defect in these B cells occurs later than the phospholipid synthesis acceleration step, or on a different pathway.
Induction of IgG and IgE synthesis in normal B cells by autoreactive T cell clones.
Authors: Leung D Y , Young M C , Geha R S 
Published: December 2022

Abstract
During the course of generating tetanus toxoid (TT)-specific T cell clones frm an HLA-DR2,7 donor, four clones were obtained which proliferated in the presence of autologous monocytes alone without the addition of TT antigen. This proliferation was specifically inhibited by anti-HLA-DR framework mouse monoclonal antibody, and appeared to be HLA-DR-restricted. Two of the clones proliferated in response to HLA-DR2-bearing monocytes, and the other two clones proliferated in response to HLA-DR7-bearing monocytes. The capacity of these four autoreactive human T cell helper clones to induce IgE synthesis in B cells was studied. All four clones stimulated autologous peripheral blood B cells to synthesize IgE and IgG antibody. Induction of IgE synthesis in B cells by the autoreactive T cell clones followed the same pattern of HLA-DR restriction which governed the proliferative response of these clones. These results suggest that the interaction of autoreactive helper T cells with B cell HLA-DR antigens may be important in the activation of IgE immune responses in humans.
Monoclonal antibody-mediated inhibition of interferon-gamma-induced macrophage antiviral resistance and surface antigen expression.
Authors: Vogel S N , Havell E A , Spitalny G L 
Published: December 2022

Abstract
A monoclonal antibody (MAb) with specificity for murine interferon-gamma (IFN-gamma) was used as a probe for studying the effect of recombinant IFN-gamma (rIFN-gamma) on antiviral activity, Fc receptor expression, and Ia antigen induction in macrophages. Cultures of C3H/HeJ peritoneal exudate macrophages were used to allow direct comparison of all three functions in the same target cell system. Our data provide two major findings: the efficacy of the MAb is very different depending on whether murine fibroblasts or macrophages are used as the target cell in the antiviral assay, i.e., greater than 20 to 100 times more MAb was required to block antiviral activity in macrophage cultures; and 10 to 50 times more MAb was required to inhibit Fc receptor vs Ia antigen expression in response to rIFN-gamma. These latter findings confirm and extend previous observations, which indicate that the induction pathways of two important differentiation markers by IFN-gamma may be dissociable.
An assay for colony-stimulating factor (CSF) production by single T lymphocytes: estimation of the frequency of cells producing granulocyte-macrophage CSF and multi-lineage CSF within a T lymphocyte clone.
Authors: Kelso A 
Published: December 2022

Abstract
The frequency of cells producing hemopoietic colony-stimulating factors (CSF) in a murine T lymphocyte clone has been determined by using a simple microassay that does not require clonal expansion or the addition of accessory cells. When stimulated with concanavalin A (Con A), the clone LB3 produced both granulocyte-macrophage CSF (GM-CSF) and multi-lineage CSF (Multi-CSF), which could be detected by using the cell line FDC-P1, whose proliferation is dependent on the presence of either of these factors. Limiting dilution analysis of Con A-stimulated LB3 cells indicated a requirement for cell-cell contact for optimal production of CSF, which could be bypassed by preincubation of the cells at high density with Con A for 4 hr before dilution in the assay. Limiting dilution estimates of the frequency of CSF-producing cells among Con A-pretreated LB3 cells ranged from 20 to 50%. Direct measurement of CSF production by single Con A-pretreated cells isolated by micromanipulation revealed that 10 to 20% could secrete detectable CSF. However, when isolated Con A-pretreated two-cell and three-cell aggregates were assayed, 50 to 99% were positive, indicating that 30 to 80% of the cells in the aggregates secreted CSF. Assay of the supernatants from single cells and two-cell aggregates on both FDC-P1 cells and another cell line, 32D c13, which responds only to Multi-CSF, demonstrated that many cells produced GM-CSF only, and others varied in the relative quantities of GM-CSF and Multi-CSF produced.
A phenyl-beta-galactoside-specific monoclonal antibody reactive with murine and rat NK cells.
Authors: Miller V E , Lagarde A E , Longenecker B M , Greenberg A H 
Published: December 2022

Abstract
The phenyl-beta-galactoside (phi-beta-gal)-specific monoclonal antibody (mAb) 49H.8 cross-reacts with the terminal disaccharide structure of the asialo GM1 (AGM1) molecule. It was found to react with phi-beta-gal determinants on murine and rat splenic natural killer (NK) cells, as measured by complement depletion studies. Flow cytometric analysis identified the antigen on two IL 2-dependent cloned murine NK cell lines and the rat large granular lymphocyte leukemia RNK. We have compared the 49H.8 reactivity to that of anti-AGM1 antisera (alpha-AGM1) on NK cells and a panel of NK related killer cells, including bone marrow-derived killer cells, lymphokine-activated killer cells (LAK), and anomalous killer cells (AK). We found that the 49H.8 specificity closely paralleled that of alpha-AGM1. When tested against Con A-reactive T cells, the 49H.8 mAb was less reactive than the alpha-AGM1, indicating that it may be a more specific marker for splenic NK populations than the alpha-AGM1.
Alternative complement pathway activation by C4b deposited during classical pathway activation.
Authors: Matsushita M , Okada H 
Published: December 2022

Abstract
Sheep erythrocytes (E) sensitized with anti-E antibody (A) were reacted with guinea pig C1 (C1gp) and human C4 (C4hu) or guinea pig C4 (C4gp) to prepare EAC1, 4b. Treatment of the EAC1, 4b with a buffer containing EDTA removes C1rgp and C1sgp, resulting in the formation of EAC4b. EAC4b prepared in this way were found to be lysed by human or guinea pig serum in a gelatin Veronal-buffered saline containing 2 mM MgCl2 and 8 mM EGTA (Mg-EGTA-GVB). In the hemolytic sensitivity of EAC4bhu, essentially no difference was noted whether IgG or IgM antibodies were used for preparation of EAC4bhu. The extent of the hemolysis of EAC4bhu was dependent on the dose of C4bhu. Because EAC4bhu were lysed even by C2-deficient human serum, C3 convertase of the classical complement pathway would not be involved in the hemolysis of EAC4bhu. Furthermore, the reactivity of EAC4bhu with serum in Mg-EGTA-GVB remained even after treatment of the intermediate cells with 1 mM PMSF, indicating that any remaining C1gp was not responsible for the hemolysis. Therefore, the hemolysis of EAC4b by sera in Mg-EGTA-GVB was considered to be mediated via activation of the alternative complement pathway (ACP). Pretreatment of EAC4bhu with anti-C4hu antibody or C4-binding protein suppressed the hemolysis of EAC4bhu via the ACP activation. Furthermore, EAC4bhu were more sensitive to hemolysis by the reaction with a mixture of C3, B, D, and H followed by rat serum in EDTA-GVB than EAC1qgp were. These results indicate that C4b molecules on the cell membrane participate in the activation of ACP.
Interleukin 1: a common endogenous mediator of inflammation and the local Shwartzman reaction.
Authors: Beck G , Habicht G S , Benach J L , Miller F 
Published: December 2022

Abstract
In this study we investigated the role of interleukin 1 (IL 1) in the induction of inflammatory lesions and in the preparation and provocation of the local Shwartzman reaction. Both of these phenomena can be induced with a variety of agents. This suggested to us that a common endogenous mediator may be crucial to the development of these two lesions. When IL 1 was injected intradermally into shaved rabbit backs, 51Cr-labeled neutrophils accumulated at the injection site. Neutrophils began to accumulate less than 1 hr after injection, and the maximum rate of accumulation was observed by 4 hr. This activity was dose dependent. It was calculated that in all animals, 10(-14) mol of IL 1 induced significant neutrophil accumulation, whereas in many animals, as little as 10(-15) mol of IL 1 sufficed. When 4.2 X 10(-9) mol of E. coli 0111:B4 lipopolysaccharide W was injected i.v. 24 hr after an intradermal injection of IL 1 (2.9 X 10(-13) mol), a local Shwartzman reaction was seen 4 hr later at the intradermal injection site. IL 1 injected i.v. 24 hr after an intradermal injection of either IL 1 or lipopolysaccharide also produced a local Shwartzman reaction. These data indicate that IL 1 may be the common endogenous mediator of the inflammatory response, and IL 1 may serve in the same role for the preparation and provocation of the local Shwartzman reaction.
The enhancing effect of interferon-beta and -gamma on the killing of Leishmania tropica major in human mononuclear phagocytes in vitro.
Authors: Passwell J H , Shor R , Shoham J 
Published: December 2022

Abstract
Both native human IFN-beta or -gamma added to human monocytes in culture increased their leishmaniacidal effect on intracellular Leishmania tropica major (L. major) amastigotes. This effect was dose-dependent, and was apparent if the IFN was added either before or after infection of the monocyte cultures with the promastigote form of the parasite. Compared on the basis of antiviral activity, IFN-gamma was shown to have a leishmaniacidal effect approximately three times greater than IFN-beta. Recombinant IFN preparations showed similar effects. In addition, IFN-gamma increased H2O2 production from human monocytes in culture in a dose-dependent manner. Monoclonal antibody to IFN-gamma abrogated both its effect on the leishmaniacidal capacity and on H2O2 production by the monocytes. These results suggest that IFN-gamma may be of therapeutic value in cutaneous leishmaniasis.
Natural and recombinant human interleukin 1-beta is cytotoxic for human melanoma cells.
Authors: Lachman L B , Dinarello C A , Llansa N D , Fidler I J 
Published: December 2022

Abstract
Human peripheral blood monocytes stimulated with LPS were found to release an activity that was cytotoxic for the A375 melanoma. Biochemical and immunological characterization of the activity indicated that IL 1-beta was the cytotoxic agent. Human recombinant IL 1-beta, purified to homogeneity, was directly cytotoxic for A375. Tumor necrosis factor, also released by activated monocytes, was not cytotoxic for the A375 melanoma.
Phenotypic alterations in tumors that developed from threshold subcutaneous inocula. I. Reduced binding of natural antibodies and sensitivity to hypotonic lysis.
Authors: Brown G W , Lesiuk T P , Chow D A 
Published: December 2022

Abstract
Tumors obtained from the injection site of threshold subcutaneous inocula of L5178Y-F9 or SL2-5 lymphomas in syngeneic mice exhibited increased tumor frequencies and reduced sensitivities to other parameters of natural immune resistance in vivo and in vitro. An examination of the resistant phenotype of cells derived through this model of tumor progression revealed that the more aggressive in vivo grown cells were less able to inhibit natural killer (NK) cell cytolysis and to bind natural antibodies (NAb) measured through fluorescence analysis, although they could not be distinguished from the starting clones by absorption of NAb for complement-mediated lysis. The in vivo grown cells also exhibited a reduced sensitivity to hypotonic lysis, which was not detectable after preincubation at 4 degrees C or upon exposure to sodium azide, procedures that reduced the lysis of the starting clones. The differential susceptibility of the in vivo grown cells was increased to control levels by treatment with cycloheximide or colchicine. These studies suggest that a decreased sensitivity to lysis associated with a reduced autolytic process and an increased counterlytic mechanism, in addition to a reduced antigen expression for binding of NK cells and certain NAb contribute to this resistant phenotype, which may characterize tumors that arise under the selective pressure of natural resistance mechanisms in the natural course of neoplastic development.
Interferon-gamma induction of LFA-1-mediated homotypic adhesion of human monocytes.
Authors: Mentzer S J , Faller D V , Burakoff S J 
Published: December 2022

Abstract
Cell-cell adhesion plays an important role in monocyte function. To investigate the molecular basis for monocyte adhesion, we used recombinant interferon-gamma to induce the formation of homotypic monocyte adhesions. The induction of homotypic adhesions correlated with the increased expression of the LFA-1 membrane molecule. LFA-1 surface expression was increased twofold, whereas expression levels of other monocyte surface molecules including CR3 and p150,95 were unchanged. The direct involvement of LFA-1 in monocyte adhesion was addressed by anti-LFA-1 monoclonal antibody inhibition of homotypic adhesions. Two monoclonal antibodies to distinct epitopes on the LFA-1 alpha-chain completely inhibited homotypic adhesions. Antibodies to a variety of other monocyte surface molecules, often present at higher cell surface density than LFA-1, did not inhibit homotypic adhesion. A panel of monoclonal antibodies that recognized different functional epitopes on the LFA-1 alpha-chain inhibited homotypic monocyte in a hierarchy identical to that observed in previous studies of cell-mediated cytotoxicity. These findings suggest that LFA-1 serves an adhesive function for human mononuclear phagocytes. In addition to providing a molecular basis for homotypic monocyte adhesions, the results suggest a more general role for LFA-1 in monocyte adhesion reactions.
Activated suppressor cell dysfunction in progressive multiple sclerosis.
Authors: Antel J P , Bania M B , Reder A , Cashman N 
Published: December 2022

Abstract
Concanavalin A (Con A)-induced suppressor activity has previously been shown to be reduced in multiple sclerosis (MS) patients with active clinical disease. In this study, we demonstrate that OKT3, as well as Con A induced suppressor activity mediated by unfractionated peripheral blood mononuclear cells is reduced in patients with the progressive form of MS. By performing reconstitution experiments involving E+, T4+, or T8+ cells derived from either MS patients or controls, and normal allogeneic macrophages or E- cells, we sought to define the cellular basis for this suppressor defect. In both MS and control groups, E+ cells were required to obtain measurable levels of suppression. Suppressor levels induced by Con A-activated cultures containing E+ cells from MS patients were lower than those induced by those containing control donor E+ cells. Suppression mediated by T8+ cells from MS patients was also lower than for controls. In the control group, suppression mediated by T8+ cells exceeded that mediated by T4+ cells; such differences were not apparent in the MS group. These results suggest that although Con A-induced suppression can be mediated by a number of T and non-T cell subsets, the functional suppressor defect measured in the MS population does involve the T8+ cell subset.