bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation.
Authors: Morrissey P J , Conlon P , Braddy S , Williams D E , Namen A E , Mochizuki D Y 
Published: December 2022

Abstract
Lymphopenia was induced in mice by a single injection of cyclophosphamide. IL-7 or a control protein were administered to the mice twice daily and the cellularity and composition of the spleen, lymph node, bone marrow, and thymus were determined at various time points thereafter. In comparison to the control cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity. There was no significant difference in the rate of recovery of the bone marrow and thymus of the control and IL-7-treated mice. Assessment of the pre-B cell compartment revealed a dramatic increase in total pre-B cell numbers in the spleen and bone marrow of the IL-7-treated mice as measured by both flow microfluorimetry and a pre-B cell colony-forming assay. This was followed in a few days by a significant increase in surface IgM+B cell numbers to levels above normal values in both the spleen and lymph node. IL-7 administration to cyclophosphamide-treated mice also resulted in an accelerated recovery of peripheral CD4+ and CD8+ cell numbers in the spleen and lymph node. The numbers of CD8+ cells were increased by twofold over normal levels in cyclophosphamide-treated mice receiving IL-7. Myeloid recovery was determined in cyclophosphamide treated mice by assessing the numbers of CFU-granulocyte-macrophage and Mac 1+ cells. There was no significant difference in myeloid recovery between cyclophosphamide-treated mice receiving IL-7 or control protein. These results suggest that administration of IL-7 after chemical-induced lymphopenia may have therapeutic benefits in shortening the period required to achieve normal lymphoid cellularity.
Phosphoinositide breakdown is associated with Fc-gamma RII-mediated activation of 5'-lipoxygenase in murine eosinophils.
Authors: De Andres B , Del Pozo V , Cardaba B , Martin E , Tramon P , Lopez-Rivas A , Palomino P , Lahoz C 
Published: December 2022

Abstract
In this report we present data on the ability of murine eosinophils to generate inositol phosphate derivatives, and their relationship with the activation of 5'-lipoxygenase by a Fc-gamma R-dependent mechanism. The addition of anti-IgG F(ab')2 to mouse eosinophils, previously sensitized with IgG, induces inositol phosphate generation after 2 min and after 10 min of stimulation. Maximal generation of inositol tris and inositol tetrakis phosphate has been detected after 15 min of stimulation, and the optimal concentration of anti-IgG F(ab')2 was found to be 25 micrograms. Inositol tris phosphate formation is also observed at 5 min after the addition of the calcium ionophore A23187 (5 microM). We also report that neomycin, an inhibitor of phosphoinositide-phospholipase C, inhibits Fc-gamma R-mediated phosphoinositide breakdown in a dose-dependent manner (88% inhibition at 150 microM of neomycin). The possible involvement of phosphoinositide breakdown in the activation of 5'-lipoxygenase has been investigated. Using streptolysin-O permeabilized cells and different doses of neomycin that inhibit phosphoinositide breakdown, we have demonstrated a parallel decrease in LTC4 released by these cells, using either A23187 (86% inhibition at 200 microM of neomycin) or anti-IgG F(ab')2 (82.4% inhibition at 100 microM of neomycin). [Ca2+]i elevation has been observed by loading the cells with the fluorescent calcium indicator Fura-2 penta-acetoxy methyl ester and after stimulating with the anti-Fc-gamma RII mAb (2.4G2). It is likely that the activation of murine eosinophils by a Fc-gamma R mechanism stimulates phosphoinositide breakdown as a primary step that leads to the activation of murine 5'-lipoxygenase, producing the formation of leukotriene C4.
Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation.
Authors: Lanier L L , Yu G , Phillips J H 
Published: December 2022

Abstract
Two genes encode Fc gamma RIII (CD16), a low affinity FcR for IgG. CD16-I is expressed as a phosphatidylinositol glycan-anchored membrane glycoprotein on neutrophils, whereas CD16-II is a transmembrane-linked glycoprotein on NK cells. Membrane anchoring is determined by codon 203. Site-directed mutation of codon 203 and transient expression of these cDNA in COS-7 cells indicated that Phe, Ile, Leu, and Val permit transmembrane expression, whereas Ser, Thr, Tyr, Asn, Gly, Ala, Asp and Lys enable phosphatidylinositol-glycan attachment. Thus, the involvement of amino acid 203 in membrane anchoring cannot be explained simply on the basis of size, charge, or polarity of the amino acid side groups at this site. Efficient expression of CD16-II in COS-7 cells requires co-transfection with either CD3 zeta or Fc epsilon RI-gamma. Truncation of the cytoplasmic segment of CD16 failed to affect association with CD3 zeta. CD3 zeta and Fc epsilon RI-gamma with truncated cytoplasmic segments were also able to facilitate membrane expression of CD16-II, implicating the transmembrane segments as the interaction site between CD16-II and CD3 zeta or Fc epsilon RI-gamma. Prior studies have suggested that the acidic residue in the CD3 zeta transmembrane segment may be important for the association of CD3 zeta complexes. Although site-directed mutation of CD3 zeta-Asp36 to Glu, Leu, or Val retained the ability to permit membrane expression of CD16-II, quantitatively the wild-type CD3 zeta-Asp36 provided optimal levels of expression, consistent with conservation of this amino acid in mouse and human CD3 zeta.
Binding to native proteins by antipeptide monoclonal antibodies.
Authors: Spangler B D 
Published: December 2022

Abstract
mAb raised against synthetic peptides derived from cholera toxin, myohemerythrin, and sickle hemoglobin were analyzed by both solid-phase and solution-phase methods. Antipeptide mAb against cholera toxin (mAb TE32 and TE33), against myohemerythrin (mAb B13I2, B13C2, and B13F2), and against sickle hemoglobin (mAb HuS-1 and HuS-2), had been previously described and used for vaccine development, structural characterization, or identification of a specific antigenic determinant, and each was apparently capable of binding both peptide and native Ag. In this study, all were found to bind whole protein when tested against immobilized Ag in a standard solid-phase assay (ELISA), yet none of the antibodies recognized the Ag in its true native form, failing to bind when tested in several solution-phase assay systems, including size exclusion HPLC. This discrepancy may be the result of modifications of the epitope created by interaction and possible denaturation of the protein on the solid-phase matrix. As a consequence, binding of these antibodies to peptides, either immobilized or in solution, or to immobilized protein, cannot be used to infer that the peptide has assumed a conformation that corresponds to that of the cognate sequence in the native protein. A re-evaluation of binding data that relates antipeptide mAb to native structural characteristics may be necessary.
The development of competence in resting B cells. The induction of cyclic AMP and ornithine decarboxylase activity after direct contact between B and T helper cells.
Authors: Pollok K E , O'Brien V , Marshall L , Olson J W , Noelle R J , Snow E C 
Published: December 2022

Abstract
In the present communication, an experimental approach is utilized that facilitates the study of biochemical processes induced in B cells after their interaction with Th cells. In this approach, Th cell clones are stimulated for 18 h upon anti-CD3-coated plates, fixed with paraformaldehyde, and added at a 2 to 3:1 ratio to small, resting B cells (isolated from Percoll gradients). Th cells not stimulated on anti-CD3-coated plates, but fixed with paraformaldehyde, serve as controls for these experiments. The activated, fixed Th cells induce a transient, sixfold increase in B cell levels of cAMP, as well as an increase in B cell expression of ornithine decarboxylase (ODC) activity. This enzyme initiates the synthesis of polyamines and has been shown to be increased as cells enter the growth phase. In addition, previous studies have shown that the cellular levels of ODC activity are controlled by a multi-tiered regulatory cascade. To examine this aspect, polyclonally stimulated B cells were studied. Such cells demonstrated a gradual increase in ODC mRNA levels that peaked between 6 and 15 h and can be partially explained by a three- to fourfold increase in mRNA stability but not by changes in the enzyme affinity for substrate. The increase in ODC mRNA occurs in the absence of protein synthesis, suggesting that the ODC gene is a member of the immediate/early gene family. Finally, the early increase in ODC mRNA was enhanced in cells in which cAMP levels were artificially elevated, suggesting the possibility that the cAMP-dependent signaling pathway participates during the regulation of this gene expression. The significance of these experimental results concerning the process of B cell activation is discussed.
The accessory function of murine intercellular adhesion molecule-1 in T lymphocyte activation. Contributions of adhesion and co-activation.
Authors: Kuhlman P , Moy V T , Lollo B A , Brian A A 
Published: December 2022

Abstract
These studies demonstrate that the murine intercellular adhesion molecule-1 (ICAM-1) performs at least two roles in enhancing T cell activation. These two roles are evident in both of our experimental systems: with ICAM-1 expressed on the surface of transfected fibroblast cells, and with purified ICAM-1 immobilized on plastic. First, as has been documented by many investigators, ICAM-1 mediates adhesion between ICAM-1- and lymphocyte function-associated Ag-1 (LFA-1)-bearing cells. This adhesive interaction occurs even in the absence of T cell stimulation, although it is increased by addition of phorbol ester and calcium ionophore. Although ICAM-1 expression does markedly increase intercellular adhesion, the increase is significantly less than the improvement ICAM-1 expression makes in the Ag-presenting ability of MHC class II-transfected fibroblast cells. We have investigated whether this difference is due to LFA-1-mediated signaling, and we present data that demonstrates that although ICAM-1 does not deliver costimulatory signals required for T cell activation, the interaction of LFA-1 with ICAM-1 does synergize with TCR-transduced signals. This synergy is observed for ICAM-1 on live and on chemically fixed accessory cells, and for purified ICAM-1 molecules, but in all cases occurs only when the ICAM-1 and the TCR ligands are on the same surface. Finally, when the ICAM-1 is present on the surface of accessory cells, it enhances T cell activation by changing the Ag dose-dependence of the T cell, but when ICAM-1 and CD3 mAb are co-immobilized, ICAM-1 increases the peak response of the T cell without affecting the dose dependence of the response.
Suppression of the immune response to immunotoxins with anti-CD4 monoclonal antibodies.
Authors: Jin F S , Youle R J , Johnson V G , Shiloach J , Fass R , Longo D L , Bridges S H 
Published: December 2022

Abstract
Treatment of normal mice with a mAb to CD4 (GK1.5) was explored as a means of inhibiting the antibody response to an immunotoxin. Three days of pretreatment with 200 micrograms of GK1.5 completely abrogated the primary antibody response to a 3-micrograms dose of a mutant diphtheria toxin conjugated to an anti-transferrin receptor antibody. The same dose and schedule of anti-CD4 antibody significantly reduced and delayed, but did not prevent, the anamnestic antitoxin response in animals that had been previously primed to the immunotoxin. Three daily injections of anti-CD4 antibodies followed by weekly doses of immunotoxin resulted in a 3-wk delay in the development of antitoxin antibodies, and the kinetics of the antitoxin response correlated with the kinetics of recovery of CD4+ T cells in the spleen and lymph nodes. The antitoxin response to repeated doses of immunotoxin was completely abrogated when anti-CD4 antibodies were given every 2 wk throughout the course of immunotoxin treatment. Thus, transient depletion of Th cells during treatment can block the immune response to an immunotoxin. There was no evidence of tolerance induction with this regimen.
Regulation of granulomatous inflammation in murine schistosomiasis. V. Antigen-induced T cell-derived suppressor factors down-regulate proliferation and IL-2, but not IL-4, production by CD4+ effector T cells.
Authors: Fidel P L , Boros D L 
Published: December 2022

Abstract
Acute murine schistosomiasis mansoni is characterized by a vigorous CD4+ delayed-type hypersensitivity T cell-mediated granulomatous immune response to deposited parasite eggs. During the chronic stage of infection the granulomatous response is spontaneously down-modulated by Ag-specific Ts cells and their soluble factors. Recently, we established an in vitro model system whereby soluble egg Ag (SEA)-induced acute and chronic infection-derived Ts cells suppressed the proliferation and IL-2 production of acute infection effector delayed-type hypersensitivity T cells. In the present study, culture supernatants harvested from the induced Ts cell cultures were found to suppress, in a non-cytotoxic manner, the SEA-mediated proliferation and IL-2, but not IL-4 production of acute infection CD4+ splenic T cells. Northern blot analysis confirmed that the factor-mediated suppression of IL-2 in the acute infection cells occurred at the transcriptional level as IL-2 mRNA was suppressed within 10 h of SEA stimulation. The acute (A-TseF) and chronic (C-TseF) infection-derived effector suppressor factors were found to be Ag-specific both in production and elicitation of function, and acted without MHC restriction. Moreover, the A-TseF and C-TseF molecules bear binding sites for SEA and an A-TseF was also shown to bind anti-SEA antibodies. Positive selection by flow cytometry showed that the TseF molecules are produced by Ag-stimulated CD4+ acute or chronic infection splenic cells and that CD4+ cells are the target of the suppression.
Mutational analysis of regulation of MHC and anti-viral genes.
Authors: Rodgers J R , Wyde P R , Rich R R 
Published: December 2022

Abstract
CTL-mediated selection for loss of expression of Mta by H-2-heterozygous SV40-transformed mouse fibroblasts (line 24SV) produced an unusual phenotypic class of maternally transmitted Ag negative mutants defective in both MHC expression and in anti-viral activity. Severely reduced surface expression of class I MHC Ag from multiple loci of both haplotypes correlated with low levels of MHC H chain and beta 2-microglobulin mRNA. Inasmuch as IFN can up-regulate class I expression and some fibroblasts elaborate autocrine IFN-beta, we examined whether IFN could restore wild-type expression of class I MHC Ag. However, IFN could not restore wild-type expression. Moreover, the fold-increases in class I Ag and mRNA expression were significantly reduced in mutant cells compared to wild-type cells. These results suggested that the mutants might have generalized defects in IFN response. Inasmuch as the induction of an anti-viral state is a hallmark of IFN responses, we exposed cells to IFN-alpha, -beta, or -gamma and challenged with virus. 24SV cells, exposed to any of the three IFNs, were completely protected from destruction by vesicular stomatitis, mengovirus or respiratory syncytial viruses. In contrast, MHC and anti-viral defective mutants could not be protected from virus-induced lysis by any IFN. Somatic cell hybridization analyses indicated that both basal MHC and IFN-inducible phenotypes were recessive to wild-type, and that a trans-acting regulatory factor required for basal MHC expression is defectively expressed in the mutants. Such a factor may integrate the organismal response to virus infection, encompassing both immune and nonimmune anti-viral responses.
An analysis of the role of guanine nucleotide binding proteins in antigen receptor/CD3 antigen coupling to phospholipase C.
Authors: Graves J D , Cantrell D A 
Published: December 2022

Abstract
In permeabilized human T lymphocytes, phospholipase C (PLC)-mediated metabolism of polyphosphatidylinositols can be stimulated by triggering the T cell antigen receptor/CD3 antigen complex (Ti/CD3) with the CD3 antibody UCHT1 or by activation of G proteins with the non-hydrolyzable guanine nucleotide analogue, guanosine 5'-O-(3-thiotrisphosphate) (GTP[S]). Ti/CD3 induction of inositol phosphate production demonstrated no dependence on exogenous guanine nucleotides. Furthermore, Ti/CD3 stimulation did not influence the kinetics or dose-response of GTP[S]-induced inositol phosphate production, suggesting that the Ti/CD3 complex does not regulate guanine nucleotide exchange on the G protein pool stimulated by GTP[S]. These data indicate that the Ti/CD3 complex is not G protein-linked to PLC in a manner analogous to the G protein linkage of receptors to adenylate cyclase. However, the inhibitory guanine nucleotide, GDP, antagonizes not only GTP[S]-induced polyphosphatidylinositol hydrolysis but also UCHT1-induced inositol phosphate production. These data infer that a G protein can modulate the coupling of the Ti/CD3 complex to PLC and that there may be some "cross-talk" between Ti/CD3 and G protein PLC coupling mechanisms.
Repopulation of host lymphohematopoietic systems by donor cells during graft-versus-host reaction in unirradiated adult F1 mice injected with parental lymphocytes.
Authors: Hakim F T , Sharrow S O , Payne S , Shearer G M 
Published: December 2022

Abstract
The graft-vs-host reaction (GVHR) generated by the injection of parental lymphocytes into unirradiated immune-competent F1 hosts is characterized by an acute loss of immune functions, an attack on host tissues, and a gradual recovery of function. Flow cytometric analysis of the donor- and host-derived splenic populations during the course of acute dysfunction and gradual recovery revealed a complex pattern of changes in lymphoid and myeloid populations that resulted in the repopulation of the host with donor-derived cells. Initially, donor-derived T cell populations expanded, particularly CD8+ T cells. Next, host T cell and B cell populations disappeared. Finally, donor-derived cells repopulated the lymphohematopoietic system in the sequence myeloid populations, B cells, and, after a protracted period, T cells. The recovery of immune functions following GVHR-induced immune deficiency was associated with this repopulation of the spleen by donor-derived cells. Donor repopulation of the host lymphohematopoietic system required the presence of both CD4 and CD8 cells in the original donor inoculum. Depletion of donor CD4 populations precluded development of GVHR or any donor engraftment; depletion of CD8 cells resulted in engraftment solely of donor CD4 populations.
T-dependent destruction of thyroid isografts exposed to IFN-gamma.
Authors: Frohman M , Francfort J W , Cowing C 
Published: December 2022

Abstract
Several autoimmune diseases are accompanied by tissue-specific expression of class II molecules of the MHC, and it has been suggested that this elicits a T cell response against tissue-specific Ag to which the individual is not tolerant. However, recent transgenic studies have indicated that non-lymphoid expression of class II genes in the pancreas, liver, and kidney is either innocuous or induces peripheral tolerance. To test this hypothesis in another organ-specific autoimmune disease, we attempted to induce autoimmune thyroiditis in normal mice with class II+ thyroid tissue. Normal thyroid lobes were cultured with and without IFN-gamma and then transplanted to adult isogeneic recipients. The thyroid that had been induced to express class II genes by IFN-gamma was destroyed in normal mice, whereas the control cultured thyroid and the native cervical gland survived. Both types of transplants remained intact and functional in congenic nu/nu recipients, indicating that neither exposure to IFN-gamma nor expression of class II genes compromised the thyroid. Thus, in some tissues, exposure to IFN-gamma and/or the induction of class II expression can lead to T-dependent autoimmune disease.
Binding and complement activation by C-reactive protein via the collagen-like region of C1q and inhibition of these reactions by monoclonal antibodies to C-reactive protein and C1q.
Authors: Jiang H X , Siegel J N , Gewurz H 
Published: December 2022

Abstract
Ligand-complexed C-reactive protein (CRP), like aggregated or complexed IgG, can react with C1q and activate the classical C pathway. Whereas IgG is known to bind to the globular region and not to the collagen-like region (CLR) of C1q, the site of interaction of C1q with CRP has not been defined. CRP-trimers were prepared by cross-linking and found to bind to C1q and to activate the C system. Heat-aggregated IgG (Agg-IgG) did not block the binding of CRP-trimers to C1q, nor did CRP-trimers block binding of Agg-IgG to C1q, suggesting that CRP and IgG bind at different sites. ELISA and Western blot analysis showed that CRP-trimers bound to the CLR, whereas Agg-IgG bound only to the globular region; similarly, anti-CLR mAb inhibited binding of CRP-trimers to C1q whereas anti-globular region mAb did not. Reactivity with CRP-trimers as well as with Agg-IgG was retained after reduction/alkylation and SDS treatment of C1q. A group of 22 anti-CRP mAb directed against at least six distinct native-CRP epitopes and eight distinct neo-CRP epitopes was tested for ability to inhibit the CRP-CLR interaction; one mAb, anti-native CRP mAb 8D8, with strong inhibitory activity was identified. Fab' of 8D8 blocked binding of CRP-trimers to intact C1q as well as CLR, and also inhibited CRP (CRP-trimers and CRP-protamine complexes) induced C activation, but had no effect on C1q binding or C activation by Agg-IgG. These results indicate that a conformation-determined region on CRP binds to a sequence-determined region on the CLR of C1q in an interaction which leads to C activation. Anti-CRP and anti-C1q mAb that specifically inhibit this interaction are described.
Autoantibodies to the centrosome (centriole) react with determinants present in the glycolytic enzyme enolase.
Authors: Rattner J B , Martin L , Waisman D M , Johnstone S A , Fritzler M J 
Published: December 2022

Abstract
Autoantibodies to cellular Ag are found in the sera of patients with systemic rheumatic diseases. Identification and characterization of the reactive autoantigens has helped clinicians to define subsets of rheumatic diseases and has assisted biologists in defining the function within the cell of these molecules. We have studied autoantibodies from patients that react with the centrosome (centriole) region of the cell. We found by immunoblotting techniques that these antibodies react with a 48-kDa protein. Additional immunoblotting and affinity purification studies indicate that the Ag may be the glycolytic enzyme enolase.