bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective idiotype suppression of an adoptive secondary antiacetylcholine receptor antibody response by immunotoxin treatment before transfer.
Authors: Brown R M , Krolick K A 
Published: December 2022

Abstract
Acetylcholine receptor (AChR)-immune lymph node cells were treated with Id-specific immunotoxin before their transfer and antigenic challenge in adoptive recipient rats. In contrast to untreated, AChR-immune lymph node cells that, when challenged, produced high titers of serum anti-AChR antibody, in vitro anti-Id-ricin A chain treatment significantly inhibited anti-AChR antibody responses upon adoptive transfer. The inhibition was specific in that control lymph node cells immune to keyhole limpet hemocyanin were unaffected and totally responsive after treatment by the same immunotoxin. Furthermore, evidence is presented by isoelectric focusing analysis that the anti-Id antibody preparation used in this study contains all of the specificities required to eliminate the entire spectrum of AChR-reactive B cell clones.
Selective effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and corticosteroid on in vitro lymphocyte maturation.
Authors: Luster M I , Germolec D R , Clark G , Wiegand G , Rosenthal G J 
Published: December 2022

Abstract
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the corticosteroid dexamethasone have potent effects on lymphocyte function, although the effects of the former have not been well characterized. In the present studies murine B cell maturation was used as a model system to examine and compare the effects of TCDD and dexamethasone on cell function. Immunosuppression by TCDD and dexamethasone is mediated by binding to specific intracellular R referred to as the Ah and glucocorticoid R, respectively. Although both compounds were comparable in their ability to inhibit antibody responses to the T-independent antigen TNP-LPS, the events responsible for suppression were found to be distinct. Dexamethasone, although affecting multiple stages of B cell maturation, had its primary effect very early, manifested by inhibition of the phosphoinositide signal transduction pathway. This was evidenced by a decrease in accumulation of inositol phosphate and surface Ia antigen expression as well as an inability to enter the cell cycle after stimulation with anti-Ig. In contrast, neither early signaling events nor proliferation were affected in B cells treated with TCDD. However, TCDD inhibited Ig secretion after stimulation of B cells with T cell-replacing factor, suggesting that TCDD modulates the differentiation of B cells into plasma cells. These differential results were confirmed by monitoring the expression of surface antigens that occur on B cells, including Ia, 7D4, and PC.2, during this maturational process. Whereas dexamethasone inhibited the expression of surface antigens that occur early in maturation (Ia and 7D4), TCDD blocked only the expression of the plasma cell marker PC.2. Although TCDD altered later stages of the B cell cycle, the presence of TCDD was required at the time of initial activation to be effective, suggesting that TCDD may interfere with early cell programming.
Selective binding of Dolichos biflorus agglutinin to L3T4-, Lyt-2- thymocytes. Expression of terminal alpha-linked N-acetyl-D-galactosamine residues defines a subpopulation of fetal and adult murine thymocytes.
Authors: Farr A G , Anderson S K , Braddy S C , Mejino J L 
Published: December 2022

Abstract
Using histochemical and immunocytochemical techniques, a lectin with nominal specificity for alpha-linked N-acetyl-D-galactosamine, Dolichos biflorus agglutinin (DBA), was found to preferentially label thymocytes with an L3T4-, Lyt-2- phenotype from fetal/newborn and adult mice. Through days 14 to 16 of gestation, virtually all thymocytes bound DBA, followed by a dramatic reduction of DBA labeling during the last 4 days of gestation, reaching adult levels of about 2 to 4% of total thymocytes. At later stages of fetal development, the DBA+ cells were confined to the subcapsular area of the thymus. This apparent loss of DBA+ cells was caused by an expansion of the thymocyte population not labeled with this lectin. Affinity purification of thymocyte cell surface components with insolubilized DBA indicated that virtually all of the lectin binding to fetal thymocytes was mediated by a 120-kDa glycoprotein. In addition to thymocytes, DBA also labeled about 5% of bone marrow cells from both normal or nude mice and a small population of spleen cells as well. These results suggest that this lectin may be useful to positively select for LT34-, Lyt-2- thymocytes, and, possibly, other immature populations within the T cell lineage.
IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses.
Authors: Finkelman F D , Katona I M , Mosmann T R , Coffman R L 
Published: December 2022

Abstract
The lymphokine IFN-gamma has been shown in vitro to stimulate IgG2a secretion and inhibit IgG1 and IgE secretion by LPS-activated B lymphocytes. To determine whether IFN-gamma has a similar isotype regulatory role in vivo, we studied the abilities of rIFN-gamma and a mAb to IFN-gamma to modify the isotypes of Ig secreted in mice injected with a goat antibody to mouse IgD, which by itself induces large increases in levels of serum IgG1 and IgE and a relatively small increase in serum IgG2a. Multiple injections of IFN-gamma substantially inhibited production of IgG1 and IgE, and stimulated production of IgG2a in affinity purified goat antibody specific for mouse IgD-treated mice; anti-IFN-gamma antibody blocked the effects of IFN-gamma and in fact enhanced IgG1 and IgE secretion and inhibited the IgG2a response in these mice. The role of IFN-gamma in the selection of isotypes of Ig produced in response to injection of mice with the bacterium Brucella abortus (BA) was also studied, because killed, fixed BA are known to stimulate IFN secretion and a predominantly IgG2a antibody response. Anti-IFN-gamma antibody strongly suppressed IgG2a secretion and stimulated IgG1, but not IgE, secretion in BA-immunized mice. BA suppressed IgG1 and IgE secretion and enhanced IgG2a secretion in affinity purified goat antibody specific for mouse IgD-injected mice; treatment of these mice with anti-IFN-gamma antibody reversed the effects of BA on IgG1 and IgG2a secretion, but not the suppressive effect of BA on IgE secretion. These observations demonstrate that IFN-gamma has an important and perhaps unique physiologic role in the stimulation of IgG2a secretion and in the suppression of secretion of IgG1, whereas bacterial antigens can suppress IgE secretion by other mechanisms in addition to IFN-gamma secretion.
Heterogeneity of immature (Lyt-2-/L3T4-) thymocytes. Identification of four major phenotypically distinct subsets differing in cell cycle status and in vitro activation requirements.
Authors: Howe R C , MacDonald H R 
Published: December 2022

Abstract
Thymocytes that bear neither Lyt-2 nor L3T4 differentiation Ag (2-4- thymocytes) contain the precursors of mature Lyt-2+ and L3T4+ T cells. In the present study, we have identified four major subpopulations of 2-4- cells in adult C57BL/6 mice that differ in surface phenotype and in situ proliferative status. Two-color immunofluorescence analysis with RL-73 (a mAb recognizing an as yet unidentified activation Ag) and PC-61 (an anti-IL-2R mAb) revealed three distinct subsets of 2-4-thymocytes: RL-73+ IL-2R- (30%), RL-73+/-IL-2R+ (45%), and RL-73- IL-2R- (25%). The RL-73+ IL-2R- subset had the highest percentage of large blasts and cycling cells, whereas the RL-73+/- IL-2R+ and RL-73- IL-2R- subsets had intermediate and low percentages, respectively, indicating that in situ proliferation correlated better with RL-73 intensity than with IL-2R expression. An additional marker, heat-stable Ag (HSA), was found to further subdivide the RL-73- population into RL-73- HSA- (10% of total 2-4-) and RL-73- HSA+ (15%) fractions. The two latter (RL-73-) subsets appeared to be more "mature" than the former since they expressed high levels of Lyt-1 and appeared later during fetal thymus ontogeny. In parallel with the phenotypic analysis, we compared the in vitro activation requirements of each of the four purified 2-4- subsets. All four populations proliferated well to the combination of phorbol ester (PMA), ionomycin, and IL-2. In response to PMA and ionomycin (without added IL-2), only RL-73- HSA-cells proliferated and this proliferation was correlated with IL-2 production. However, if IL-1 was included with PMA and ionomycin then all four populations responded. Finally, a proliferative response to Con A or mitogenic anti-Thy-1 mAb was observed only for RL-73- HSA+ and (to a lesser extent) RL-73- HSA-cells. These data indicate that each of the four phenotypically distinct subpopulations of immature thymocytes can also be distinguished on the basis of their in vitro activation requirements.
Identification of a C3b/iC3 binding protein of rabbit platelets and leukocytes. A CR1-like candidate for the immune adherence receptor.
Authors: Manthei U , Nickells M W , Barnes S H , Ballard L L , Cui W Y , Atkinson J P 
Published: December 2022

Abstract
Immune adherence is the attachment of C-bearing immune complexes via the major activation fragment of the third component of C(C3b) to C3b binding membrane proteins. On primate E, the C3b-R, termed CR1, mediates immune adherence. In nonprimates, immune adherence involves platelets instead of E. However, these functional data have not been corroborated by the identification of the binding protein. In this work, we have identified a C3b/iC3 binding protein of rabbit platelets and characterized it as a single chain structure with a Mr of 150 kDa (nonreducing) or 175 kDa (reducing). This protein binds to rabbit iC3 or C3b but not C3d. This specificity of binding and the ability to rebind to a second column of iC3- or C3b-thiol-Sepharose are comparable to human CR1. Also, a molecule with the identical Mr as well as other structural and binding characteristics is present on rabbit PBMC. No such protein was isolated from rabbit E. Our data strongly suggest that the C3b/iC3 binding protein of rabbit platelets is the homologue of human CR1. If so, this represents an interesting evolutionary switch in the tissue specific expression of the immune adherence R from platelets in the nonprimate to E in the primate.
The elevated natural killer sensitivity of targets carrying surface-attached C3 fragments require the availability of the iC3b receptor (CR3) on the effectors.
Authors: Ramos O F , Kai C , Yefenof E , Klein E 
Published: December 2022

Abstract
Human serum-treated Raji and Daudi cells were shown to bind C3 fragments on their surface as a consequence of their capacity to activate C via the alternative pathway. C3 molecules were detectable on the cell surfaces up to 24 h after serum exposure. The C3 fragment-coated cells showed increased sensitivity to spontaneous lymphocyte-mediated cytotoxicity. The effector lymphocytes involved in the enhanced cytotoxicity were NK cells with low buoyant density, carrying both CR3 and FcR. Blocking of the FcR and CR3 with F(ab)2 fragments from Leu-11c or Leu-15 mAb, respectively, did not influence the lysis of targets that did not carry C3 fragments. In contrast, the accessibility of CR3 on the effector lymphocytes was essential for the C3 fragment-mediated enhancement of cytotoxicity. In addition to the Leu-15 antibody, N-acetyl-D-Glucosamine, a compound known to block iC3b binding to CR3, also abrogated the C3 fragment-imposed effect. Our previous experiments showed that the C3 fragments bind to acceptor sites on target cells. The present experiments show that the C3 fragments fixed onto the target bind to CR3 on effector cells. These data substantiate the hypothesis that the bivalent C3 fragments, which are fixed on the targets, promote their interaction with lytic lymphocytes by bridging the two cells.
Regulation of synthesis of macrophage adhesion molecule, a heterodimeric membrane glycoprotein.
Authors: Remold-O'Donnell E 
Published: December 2022

Abstract
Macrophage adhesion molecule is a surface molecule of guinea pig macrophages and neutrophils. It is the counterpart of mouse Mac-1 and human CD11b/CD18 (Mol/OKM-1/Mac-1/Leu-CAM) and is member of a family of heterodimer glycoproteins with a common beta-subunit. Macrophage adhesion molecule is a prevalent molecule in nonactivated macrophages, but it is dramatically decreased in macrophages activated in vivo. The experimental system of activated vs nonactivated guinea pig peritoneal macrophages was used to examine the mechanisms that down-regulate synthesis of this heterodimer molecule. [35S]Methionine labeling of nonactivated macrophages and chase incubation revealed that synthesis involves separate translation of the alpha- and beta-glycopeptides of "high mannose"-containing monomeric precursors, then refolding/assembly to form a heterodimer, and, finally, a maturation process that includes conversion of carbohydrate to "complex" units. Two lines of evidence demonstrate that down-regulation in activated macrophages occurs via restriction of the alpha-species. First, pre-beta is detected at 3 h only in activated macrophages. Second, the amount of newly translated pre-alpha averaged 16% in activated macrophages relative to nonactivated macrophages, which is close to the value of 12% for the mature heterodimer. The amount of newly translated pre-beta averaged 62%. These findings identify the regulatory step as a restriction of the alpha-species at, or before, translation. A model is proposed to explain regulation of synthesis of heterodimer membrane glycoproteins.
Suppression of T lymphocyte function by measles virus is due to cell cycle arrest in G1.
Authors: McChesney M B , Altman A , Oldstone M B 
Published: December 2022

Abstract
Measles virus suppresses T lymphocyte functions in vitro. When measles virus-infected T lymphocytes are stimulated with PHA or 12-O-tetradecanoylphorbol-13-acetate, plus calcium ionophore, the cells secrete IL-2 and express the IL-2R or Tac Ag to a similar extent as uninfected cells, yet proliferation is reduced by 50 to 90%. Stimulated infected T cells also express the cell surface activation Ag 4F2, transferrin R, and HLA-DR. The secretion of IFN-gamma by infected T cells in response to PHA is not suppressed at 24 to 72 h after stimulation. Total RNA synthesis at 48 and 72 h after stimulation is reduced in infected T lymphocytes. Infectious measles virus progeny are produced during this interval. Thus infected T lymphocytes can become activated in response to mitogenic stimuli and the cells support efficient viral replication before the block in cell proliferation.
An antigen-specific helper T cell hybridoma produces an antigen-specific suppressor inducer molecule with identical antigenic fine specificity. Implications for the antigen recognition and function of helper and suppressor inducer T cells.
Authors: Zheng H , Boyer M , Fotedar A , Singh B , Green D R 
Published: December 2022

Abstract
We have previously described a T cell hybridoma, A.1.1, that responds to specific Ag (P18, a synthetic polypeptide of defined sequence) in the context of I-Ad by producing lymphokines. Herein we report that this cell also releases, into culture supernatants and ascites fluid, an Ag-specific activity that functions in the induction of suppression of anti-SRBC PFC responses. This suppressive activity requires a) Ag-non-specific accessory molecules from a T suppressor inducer factor, b) Ly-2+ T cells in the assay cultures, and c) the specific Ag (P18) conjugated to the SRBC in the assay cultures. The specificity of the A.1.1-derived activity was demonstrated by the absence of suppression in cultures containing SRBC, BSA-SRBC, or conalbumin-SRBC rather than P18-SRBC. Further, the A.1.1-derived activity bound to, and could be eluted from, P18 but not conalbumin. Using a panel of synthetic variant peptides, we have mapped the critical residues in P18 required for Ag/I-Ad induced activation of A.1.1. These peptides were tested for their ability to act as targets for the A.1.1-derived suppressive activity when conjugated to SRBC and added to assay cultures. All peptides capable of stimulating the A.1.1 T cells to release lymphokines were similarly effective in the suppressor assay. Thus, the recognition of Ag by the T cells and by the T cell-derived activity appeared to be identical. The A.1.1-derived molecule was found to be capable of inducing L3T4- T cells to act as suppressor T cells following culture. These suppressor cells were active in inhibiting anti-SRBC responses in the absence of P18 and bore the Ly-2 surface marker. Thus, it is likely that the function of this Ag-specific molecule is to induce Ly-2+ suppressor T cells and thereby cause the inhibition of the response. This function is distinct from that normally associated with helper T cells and may shed new light on the possible relationship between the cell surface T cell receptor for Ag and Ag-specific T suppressor inducer molecules.
Interactions between B lymphocyte subpopulations. Augmentation of the responses of resting B lymphocytes by activated B lymphocytes.
Authors: Uher F , Dickler H B 
Published: December 2022

Abstract
Mouse B lymphocytes were fractionated from normal T lymphocyte-depleted spleen cell populations using discontinuous percoll gradients and were stimulated with rabbit F(ab')2 anti-mouse mu-specific antibodies (anti-mu) plus the supernatant of Con A-stimulated rat spleen cells (SN) as a source of lymphokines. The responses of small (mean volume 120 mu 3), dense (greater than 1.087 specific gravity), resting (least spontaneous thymidine incorporation) B lymphocytes were augmented by irradiated (4000 rad), larger (mean volume greater than 170 mu 3), less dense (less than 1.081 specific gravity), activated (greater spontaneous thymidine incorporation) B lymphocytes. Proliferation was augmented 2- to 4-fold and polyclonal antibody-forming cell responses three- to sixfold. Maximal augmentation of the responses of 5 X 10(4) resting B cells was obtained with 10(4) activated B cells. Augmenting activity was specific for activated B lymphocytes in that responses were not augmented by irradiated thymocytes, T lymphoblasts, macrophages, or additional supernatant. B lymphocytes activated in vitro by LPS or anti-mu also had augmenting activity. Augmentation of responses was maximal only when activated B lymphocytes were added simultaneously with anti-mu. The interaction between activated and resting B lymphocytes did not appear to be genetically restricted. Interestingly, the augmenting activity of activated B cells could be reconstituted by a combination of supernatant and cell membranes from these cells but not by either alone, suggesting that two components are required, one soluble and the other membrane-bound. Thus, a functional interaction has been demonstrated between B lymphocyte subpopulations which differ in their state of activation, and this interaction appears to involve a novel mechanism of action.
Specific in vivo suppression of lymph node cell proliferation and humoral immune responses by cloned antigen-specific T suppressor cells.
Authors: Degwert J , Heuer J , Kölsch E 
Published: December 2022

Abstract
Two BSA-specific Ts cell clones have been isolated from CBA/J mice tolerized by low doses of BSA. Together with one Ts cell clone isolated from an immune animal, they have recently been characterized with regard to phenotypes and in vitro functions. In the present report the in vivo effector functions of two of them (Ts cell clones BVI/5 and HF1.MS) are described. BSA-primed lymph node cells from CBA/J mice, which had received BVI/5 or HF1.MS Ts cells at the time of immunization, do not respond to a subsequent in vitro antigenic challenge. A human gamma-globulin (HGG)-specific lymph node cell proliferation is not influenced. BVI/5 Ts cells injected into mice at the time of priming with fluorescein (Flu)-conjugated BSA or Flu-HGG inhibit the humoral anti-Flu-response in Flu-BSA-primed animals. The anti-Flu-response in Flu-HGG-primed animals is only marginally affected by BVI/5 Ts cells. The data show that it is possible to induce immunologic unresponsiveness at the humoral level by reexposing in vitro propagated Ts cell clones to their syngenic in vivo environment.
Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity.
Authors: Seki N , Sudo Y , Yoshioka T , Sugihara S , Fujitsu T , Sakuma S , Ogawa T , Hamaoka T , Senoh H , Fujiwara H 
Published: December 2022

Abstract
Immunization of DBA/1 mice with type II collagen resulted in typical and progressive arthritis, which is associated with the production of high titer of anti-collagen antibody and the induction of cell-mediated immunity as exemplified by delayed type hypersensitivity response as well as lymphokine production. In contrast, administration of heat-denatured collagen into DBA/1 mice failed to induce the arthritis. These mice produced only marginal antibody, whereas they developed comparable cell-mediated immunity to that induced by immunization with native collagen, and therefore the inoculation of heat-denatured collagen provided the regimen capable of inducing preferentially cell-mediated immunity without the generation of high level of antibody. Inasmuch as administration of antibody induced only marginal and transient joint swelling not associated with typical histologic lesion, the synergistic effect of humoral and cell-mediated immunities was investigated using antibody preparation and the regimen to induce selectively cell-mediated immunity. The results demonstrate that administration of antibody into DBA/1 mice pre-sensitized with heat-denatured collagen resulted in potent and progressive arthritis. Such synergy was further confirmed by the induction of arthritis in T cell-depleted DBA/1 mice that had been adoptively transferred with antibody and lymphoid cells from heat-denatured collagen-sensitized mice. Moreover, it was revealed that the nature of cells capable of transferring cell-mediated immunity was of Thy-1+ and L3T4+ Lyt-2-. These results indicate that anti-collagen antibody and L3T4+ T cell-mediated cellular immunity are crucially required for the perpetuated development of type II collagen-induced arthritis.
Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma.
Authors: Billiau A , Heremans H , Vandekerckhove F , Dijkmans R , Sobis H , Meulepas E , Carton H 
Published: December 2022

Abstract
Acute experimental allergic encephalomyelitis (EAE) was induced in C57BL/6J and SJL/J mice by injection of isologous spinal cord homogenate given in conjunction with Bordetella pertussis and Freund's adjuvant. SJL/J mice showed a highly aggressive and 100% lethal form of the disease; C57BL/6J mice were much less susceptible as they had low morbidity rates (20 to 40%), low disease scores, and mostly no mortality. Treatment of these low susceptibility mice with neutralizing mAb against IFN-gamma caused an increase in morbidity rates as well as significant mortality (up to 80%). Similar antibody treatment did not affect the course of the disease in the high susceptibility SJL/J mice. However, treatment of these mice with IFN-gamma resulted in reduced morbidity and mortality. A similar but less pronounced inhibition of the disease in SJL/J mice could be obtained by administration of IFN-alpha/beta or by acute infection with lactate dehydrogenase virus. The results indicate that endogenous as well as exogenous IFN can exert a down-regulating effect on the development of EAE. They also indicate that endogenous IFN-gamma is produced during the development of EAE and plays a disease-limiting role.