bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human neutrophil adherence to thrombospondin occurs through a CD11/CD18-independent mechanism.
Authors: Suchard S J , Burton M J , Dixit V M , Boxer L A 
Published: December 2022

Abstract
Thrombospondin (TSP), a 450-kDa trimeric glycoprotein secreted by platelets and endothelial cells at sites of tissue injury or inflammation, may play an important role in polymorphonuclear leukocyte (PMN) adherence to blood vessel walls before diapedesis. We have examined the adherence of PMN to TSP and compared it to adherence to other extracellular matrix proteins. PMN adherence to TSP-coated plastic was complete by 60 min with spreading completed by 2 h. The kinetics of adhesion and spreading on TSP were similar to that of vitronectin (VN), laminin (LN), and fibronectin (FN). Activation of PMN with the calcium ionophore A23187 or the chemotactic peptide FMLP increased PMN adherence to LN and FN, but not to TSP or VN, suggesting that PMN activation may differentially regulate expression of TSP and VN receptors as compared to LN and FN receptors. The specificity of PMN adherence to TSP was confirmed by competition with saturating amounts of TSP and inhibition with anti-TSP antibodies. mAb A6.1, which binds to the protease-resistant core of TSP, was the most effective in blocking PMN adherence to TSP. Using TSP proteolytic fragments, we demonstrated that the primary interaction of PMN with TSP was mediated through the 140-kDa COOH-terminal domain. Inasmuch as the 140-kDa fragment of TSP contains an Arg-Gly-Asp sequence similar to the cell recognition site of FN and VN, we determined whether RGDS peptides would inhibit PMN adhesion. RGDS did not significantly inhibit PMN adhesion to TSP, VN, or LN, but reduced PMN adhesion to FN by 50%. To determine if PMN adhesion to TSP was mediated by a beta 2 integrin receptor such as LFA-1, MO-1, or p150,95, we performed adhesion assays using PMN isolated from patients with leukocyte adhesion deficiency that lack beta 2 receptors. Leukocyte adhesion deficiency PMN exhibited normal adherence to TSP. In contrast, adherence to VN, LN, and FN was reduced by 95%. Therefore, adherence to TSP is probably not mediated by a beta 2 integrin receptor. These data contribute to the accumulating evidence that PMN can interact with extracellular matrix proteins through a CD11/CD18-independent process.
Inhibition of cytolytic lymphocytes by homologous restriction factor. Lack of species restriction.
Authors: Zalman L S , Brothers M A , Strauss K L 
Published: December 2022

Abstract
Homologous restriction factor (HRF) has been shown to inhibit complement-mediated lysis in a species-restrictive manner. Human HRF is able to block lysis by human complement but not by complement from other species. HRF has also been found in the membrane of lymphokine-activated killer (LAK) cells. When this HRF is inserted into sheep erythrocyte membranes, it is able to protect the erythrocyte from LAK cell lysis. In this report, we show that while HRF can inhibit human complement but not rat complement-mediated hemolysis, it is able to inhibit LAK cell lysis by both human and rat LAK cells. HRF is therefore a more general protective protein than has been previously thought.
Delayed-type hypersensitivity initiation by early-acting cells that are antigen mismatched or MHC incompatible with late-acting, delayed-type hypersensitivity effector T cells.
Authors: Ptak W , Herzog W R , Askenase P W 
Published: December 2022

Abstract
The elicitation of delayed-type hypersensitivity (DTH) responses in mice is mediated by the sequential activities of two different Ag-specific, Thy-1+ cells. A required early phase of elicitation is due to DTH-initiating Thy-1+ cells that are CD3- and sIg- and produce Ag-specific factors that act like IgE antibodies in that they sensitize the tissues, so that after local challenge with Ag there is release of the vasoactive amine serotonin. Released serotonin locally recruits and activates CD4+ Th-1 classical DTH effector T cells that secrete lymphokines that attract and activate a nonspecific perivascular infiltrate of circulating, bone marrow-derived leukocytes. The current study used isolated subpopulations of DTH-initiating and DTH-effector T cells to determine whether the two phases of the elicitation of DTH were entirely separate. The contact sensitivity model of DTH was used. Early-acting DTH-initiating cells, and late-acting DTH-effector T cells were either from oxazolone (OX)-immune or picryl chloride (PCl)-immune CBA or BALB/c donors and were transferred to CBA or BALB/c recipients. The results showed that DTH-initiation could be mediated by polyclonal DTH-initiating cells that were Ag mismatched or MHC incompatible with late-acting DTH effector T cells. In fact DTH-initiating cells could be both Ag mismatched and MHC incompatible with late-acting T cells. In addition, potential interactions between different cell populations were ruled out by showing that DTH-initiation could be mediated by a DTH-initiating clone that was Ag or MHC mismatched with the late-acting DTH-effector T cells. Thus, the OX-specific BALB/c clone could initiate DTH for PCl-specific CBA cells in CBA recipients if the recipients were challenged with both OX and PCl, but not when they were challenged with OX or PCl alone. We suggest, at least for the elicitation of DTH reactions in mice, that a more comprehensive description of these responses should accommodate the fact that there are early and late phase responses that each begin with Ag specificity and end with non-specific humoral factors. Inasmuch as the two Thy-1+ cells of DTH can be of different Ag specificity, this suggests that some forms of delayed and chronic inflammation, might be initiated by an immediate hypersensitivity-like immune reactivity to one set of Ag, and could be prolonged and perpetuated by delayed reactivity to another set of Ag.
Anti-idiotypic antibody response to monoclonal anti-CD4 preparations in nonhuman primate species.
Authors: Attanasio R , Allan J S , Anderson S A , Chanh T C , Kennedy R C 
Published: December 2022

Abstract
A series of mouse monoclonal anti-CD4 preparations was characterized for the ability to recognize overlapping epitopes on CD4 and to inhibit HIV/simian immunodeficiency virus (SIV) syncytium formation. Based on this characterization, mAb able to recognize CD4 epitopes overlapping the HIV binding site were selected and used to immunize nonhuman primates to elicit the production of specific anti-Id antibodies. Five baboons and five rhesus monkeys were immunized with either individual or a cocktail consisting of several monoclonal anti-CD4 preparations. All the nonhuman primates produced specific anti-Id that recognized either private or cross-reactive Id depending on the monoclonal anti-CD4 used to generate the anti-Id response. Inhibition assays were performed to ascertain the ability of: 1) soluble CD4 to inhibit the Id-anti-Id reaction and 2) the various anti-Id to inhibit the CD4-monoclonal anti-CD4 reaction. These studies demonstrated that some of the anti-Id recognized a cross-reactive Id that was associated with the Ag-combining site. In addition, some of the anti-Id weakly recognized SIV gp120 by Western blot analysis. These studies may be useful in designing experiments that may lead to a better understanding of the CD4-HIV gp120 interaction and to the production of Id and/or anti-Id reagents that might be used to manipulate this virus-receptor interaction.
The specificity properties that distinguish members of a set of homologous anti-digoxin antibodies are controlled by H chain mutations.
Authors: Near R I , Bruccoleri R , Novotny J , Hudson N W , White A , Mudgett-Hunter M 
Published: December 2022

Abstract
Five murine A/J strain anti-digoxin mAb (35-20, 40-40, 40-120, 40-140, and 40-160) have highly homologous H and L chain V regions, only differing by somatic mutation, yet differ in affinity and specificity. The availability of the VH and VL genomic clones from one hybridoma, 40-140, has now allowed studies involving in vitro mutagenesis and chain recombination among these five hybridomas. To determine the relative contributions of the mutations found in either VH or VL to the overall binding properties of these antibodies, we recombined the 40-140VH with the VL of each hybridoma. The 40-140VH gene was transfected into hybridoma variants that produce only VL. The recombinant antibodies show that the mutations present in VH, rather than in VL, affect the fine specificity properties of these antibodies, whereas, the mutations among both VH and VL chains are important in determining antigen affinity. From mutations present in VH that affect fine specificity properties, the comparison of the antibody sequences, and from the previously measured binding properties, we predicted and tested selected VH mutations for their ability to alter specificity or affinity by doing site-directed in vitro mutagenesis. The results for the somatic mutations found in this group of antibodies show: 1) VH mutations control the fine specificity properties that distinguish different members of this group; 2) in particular, VH residues 54 and 55 in CDR2 control the distinguishing characteristics of specificities between these antibodies; and 3) by mutagenesis, we had the unusual result of being able to alter Ag specificity without affecting affinity. A computer model of the 40-140 antibody binding site was generated which indicates that VH residues 54 and 55 are highly accessible.
The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo. Relationship between C5a and proteins with the characteristics of IL-8/neutrophil-activating protein 1.
Authors: Collins P D , Jose P J , Williams T J 
Published: December 2022

Abstract
An in vivo experimental peritonitis model was investigated in the rabbit using zymosan as the inflammatory stimulus. After an i.p. injection of zymosan, exudate was removed at intervals and tested in the back skin of assay rabbits. Assay rabbits received i.v. injections of 125I-albumin and 111In-neutrophils, and the local accumulation of each label was measured in response to intradermal injections of exudate samples mixed with a potentiating dose of PGE2. When peritoneal exudate samples were tested in the presence of a specific anti-C5a antibody, virtually all the edema-inducing and neutrophil chemoattractant activity was abolished in samples taken up to 2 h after the zymosan injection. Later samples, however, contained increasing levels of a non-C5a component. In C5a-depleted 6-h exudate two peaks of inflammatory activity were separated using cation exchange HPLC. Evidence is presented that C5a itself is unable to stimulate the production of these activities. Both peaks of activity appear related to IL-8/NAP-1 as they inhibited the binding of 125I-IL-8/NAP-1 to human neutrophils.
Evidence for involvement of lymphocyte function-associated antigen 1 in T cell migration to epidermis.
Authors: Shiohara T , Moriya N , Saizawa K , Gotoh C , Yagita H , Nagashima M 
Published: December 2022

Abstract
Although it is well known that in various T cell-mediated skin diseases T cells migrate preferentially to epidermis, no direct evidence has been presented in which molecules on T cells are important in directing T cell traffic to epidermis. We have previously established CD4+ autoreactive cloned T cells with a special tropism for epidermis in vitro as well as in vivo. Antibody inhibition studies demonstrated that only anti-lymphocyte function associated Ag 1 (anti-LFA-1) mAb completely inhibited the in vitro migration of the T cells toward the epidermis, whereas mAb against other T cell surface molecules had little or no effect. Monovalent F(ab) fragment of the anti-LFA-1 mAb, although less efficient, also inhibited the T cell migration. The apparent dependency of the inhibition on the anti-alpha-chain mAb suggested a major role for the alpha-chain of LFA-1 in T cell migration to epidermis. The relevance of an LFA-1-dependent mechanism to the epidermotropic migration of T cells was further strengthened by the findings that the T cell migration to epidermis was inhibited by divalent cation depletion, cytochalasin B, and low temperature. These findings indicate that the LFA-1 molecule, which is thought to be primarily involved in cell-to-cell adhesions, also plays an important role in directing T cell migration to epidermis.
Cognate interactions between helper T cells and B cells. V. Reconstitution of T helper cell function using purified plasma membranes from activated Th1 and Th2 T helper cells and lymphokines.
Authors: Noelle R J , Daum J , Bartlett W C , McCann J , Shepherd D M 
Published: December 2022

Abstract
Th physically interact with B cells and produce lymphokines that influence B cell growth and differentiation. The respective contribution of cell contact and lymphokines to induction of B cell growth and differentiation was addressed using purified plasma membranes (PM) from resting Th (PMrest) and anti-CD3-activated Th (PMCD3) together with lymphokines. Results show that PMCD3, but not PMrest, induce 10% of resting B cells to enter the G1 phase of the cell cycle, with few B cells entering G1b and S/G2. The inclusion of IL-4, but not IL-2, IL-5, or IFN-gamma, amplifies the B cell response to PMCD3 by increasing the total percentage of activatable B cells to greater than 40% and inducing B cell progression into G1b, S, and G2. Direct comparison between PMrest and PMCD3 purified from Th1 and Th2 indicate that both Th1 and Th2 induce similar levels of B cell proliferation in the presence of IL-4. Further, the lymphokine requirements for B cell proliferation induced by PMCD3 from Th1 and Th2 is indistinguishable. B cell differentiation to IgM, IgG1, and IgG2a synthesis by PMCD3 required IL-4 and IL-5. Using lymphokine conditions that supported B cell differentiation, PMCD3 purified from Th1 and Th2 induced similar levels of IgM, and IgG1. Given the functional data on PMCD3 from Th1 and Th2, the data indicate that there are no substantive differences between Th1- and Th2-derived PMCD3, and that the major differences in the ability of viable Th1 and Th2 to activate B cells is the lymphokines produced by the cells.
Comparison of the effect of IL-2 and IL-6 on the lytic activity of purified human peripheral blood large granular lymphocytes.
Authors: Smyth M J , Ortaldo J R 
Published: December 2022

Abstract
The effects of IL-6 and IL-2 on highly purified, human peripheral blood large granular lymphocytes (LGL) were investigated and compared. IL-6 enhanced LGL NK activity in a dose-dependent manner against K562, however IL-2 was a more potent stimulus of LGL NK function. Neither IL-2 nor IL-6 increased LGL cytotoxic potential in a parallel estimation of heteroconjugated antibody (anti-CD16 x anti-nitrophenyl mAb)-dependent cytotoxicity against nitrophenyl-modified YAC. Unlike IL-2, IL-6 did not significantly induce LGL lymphokine-activated killer activity, LGL proliferation, or LGL lymphokine production. In particular, IL-6 did not stimulate detectable LGL IL-2 production or IL-2R modulation, and mAb to the p75 IL-2R had no effect on IL-6 induction of LGL NK activity. Therefore, in the absence of T cells, IL-6 provided an IL-2-independent signal to LGL that resulted in augmentation of their NK activity without stimulating their proliferation or other LGL functions.
A dominant idiotype in the antibody response against the influenza virus hemagglutinin. Serum and in situ analyses.
Authors: Brown A R , Sealy R E 
Published: December 2022

Abstract
PY206 is an Id associated with a BALB/c murine mAb described as being specific for the influenza A virus hemagglutinin. However, production of this Id by BALB/c mice immunized with influenza is low. This report shows that the PY206 Id is a dominant component of the anti-influenza antibody response in C57BL/6J strain mice infected intranasally with the influenza A/Hong Kong/168/(H3N2)[R] X-31 virus. High PY206 Id expression was linked to the IgHb Ig allotype locus. PY206 Id+ antibody-forming cells were identified in situ in cryostat sections of lymphoid tissues and idiotypic heterogeneity was identified among PY206+ B cells. Uninfected adult C57BL/6J mice had PY206 Id in their serum that lacked influenza binding specificity. In situ analysis of prenatal and neonatal spleen of uninfected C57BL/6J mice showed that the expansion of PY206 Id+ B cells occurred early in development. PY206+ cells were demonstrated in the lungs of influenza-infected mice but not in normal mice, establishing the capability to study this B cell population in the lung. This model offers the opportunity to manipulate the anti-influenza A virus hemagglutinin B cell response and to study the proliferation and migration of influenza-specific B cells in their native tissue environments.
A V region mutation in a phosphocholine-binding monoclonal antibody results in loss of antigen binding.
Authors: Kobrin B J , Buhl S , Shulman M J , Scharff M D 
Published: December 2022

Abstract
A V region mutant producing an antibody that had lost the ability to bind phosphocholine was isolated from a hybridoma producing a germline encoded T15 antibody. The mutation resulted in a single aspartic acid to asparagine substitution at residue 95 of the H chain V region. This confirms that the aspartic acid at residue 95 plays a major role in Ag binding. The results also suggest that somatic cell genetic techniques can be used to generate mAb with useful changes in Ag binding.
Immunodominance: intramolecular competition between T cell epitopes.
Authors: Perkins D L , Berriz G , Kamradt T , Smith J A , Gefter M L 
Published: December 2022

Abstract
We have used an approach of linking previously characterized T cell epitopes into immunologically complex synthetic peptides in order to investigate the mechanism of immunodominance. Our results show that first, cI12-26 is highly dominant following immunization with the lambda repressor (cI) protein, but is a minor epitope in the context of the cI:NP peptide. In contrast, the dominant epitope in response to the cI:NP peptide is a new junctional epitope, which is composed of sequences derived from both the cI and influenza nucleoprotein (NP) segments of the composite peptide. Second, T cell recognition of cI:NP is not significantly altered by Ag processing, based on results from glutaraldehyde-fixed APC. Third, the relative affinities of cI and cI:NP for MHC binding are similar, based on in vitro competition, excluding competition at the level of MHC binding as the determinant of immunodominance. Taken together, these results are consistent with the hypothesis that immunodominance of cI:NP is determined by peptide conformation, which affects the configuration of peptide binding to MHC, thus altering T cell recognition. In conclusion, immunodominance is not simply a function of the primary amino acid sequence, but is a function of the context of the epitope within the protein molecule.
Expression of the Blast-1 activation/adhesion molecule and its identification as CD48.
Authors: Yokoyama S , Staunton D , Fisher R , Amiot M , Fortin J J , Thorley-Lawson D A 
Published: December 2022

Abstract
We have analyzed the induction and expression of Blast-1 at the mRNA and protein levels and demonstrated its identity with CD48. Blast-1/CD48 is expressed on a wider range of cell types, notably T cells and monocytes, than previously thought, but appears to be restricted to lymphoid and myeloid cells. Resting B and T cells express Blast-1/CD48 molecules at the cell surface; however, they lack the epitope recognized by the 17D6 mAb. Resting B cells express no detectable Blast-1/CD48 mRNA. Induction by EBV infection or stimulation with PMA, IL-4, or PHA results in increased levels of Blast-1/CD48 protein (both 6.28 and 17D6 epitopes) at the cell surface. Detailed analysis of EBV-induced expression revealed that it is due to increased steady-state levels of Blast-1/CD48 mRNA induced by transforming but not nontransforming strains of the virus. Induction by IL-1 beta, ionomycin, or suboptimal levels of PMA plus ionomycin results in increased expression of the 17D6 epitope only. In transfected Cos-7 cells Blast-1/CD48 at the cell surface expresses only the 6.28 epitope, whereas cytoplasmic molecules express both 17D6 and 6.28 epitopes. We suggest that these results are most consistent with the idea that Blast-1/CD48 molecules are complexed at the surface of resting cells and Cos-7 cells, resulting in masking of the 17D6 epitope. Activation causes dissociation of the complex, revealing the 17D6 epitope. The existence of 17D6+6.28- Blast-1/CD48 molecules was demonstrated by immunoprecipitation analysis, which also revealed that, unlike the rest of the molecules, this subset was resistant to digestion with glyosylphosphatidylinositol-specific phospholipase C.
Autoantibodies to nucleolin in systemic lupus erythematosus and other diseases.
Authors: Minota S , Jarjour W N , Suzuki N , Nojima Y , Roubey R A , Mimura T , Yamada A , Hosoya T , Takaku F , Winfield J B 
Published: December 2022

Abstract
The 110-kDa intracellular phosphoprotein (110K) described previously by this laboratory as a common IgM autoantigen in SLE and certain other systemic autoimmune disorders and viral infections is identified as nucleolin in the present investigation. Using rabbit antiserum to rat nucleolin as a probe, IgM autoantibody-reactive 110K co-migrated with human lymphocyte nucleolin in one- and two-dimensional immunoblots. Rabbit anti-nucleolin also specifically depleted autoreactive 110K from detergent lysates of human cells. Because nucleolin shares amino acid sequence similarity and/or forms dynamic particles with other prominent autoantigens, the present observation raises the possibility that the nucleolin/anti-nucleolin system may be of special significance for the development of humoral autoreactivity to nuclear Ag.
Selective stimulation of thymocyte precursors mediated by specific cytokines. Different CD3+ subsets are generated by IL-1 versus IL-2.
Authors: Gotlieb W H , Durum S K , Gregorio T A , Mathieson B J 
Published: December 2022

Abstract
The sequence of activation signals that stimulate proliferation, differentiation, and selection of mature T cell subsets from immature, dull-CD5+/CD4-, CD8- double negative (bCD5), (dCD5/DN) thymocytes are still unclear. However, it is likely that cytokines play integral roles in these events. Here we report that IL-1, in the presence of Con A, supports the proliferation and differentiation of highly purified dCD5/DN precursors into bright-CD5+ DN, CD2- lymphocytes with an apparently mature phenotype. These cells express CD3 and preferentially express the products of two TCR gene families, V beta 8 and V beta 6, whose expression is dependent on the allelic expression of the Mls-1 locus. Experiments, using DN thymocytes mixed with purified dCD5 subset of DN cells from a congenic strain of mice (i.e., expressing two different alleles of CD5) have shown that the cells that are stimulated by IL-1 and comitogen are derived from the immature dCD5 subset and not from the mature bCD5 cells contained within the DN subset. In contrast, IL-2 with the co-mitogen stimulates three- to fourfold higher levels of proliferation, from the same purified immature precursor population, and nearly a twofold increase in cell yield. However, the cells that were generated from precursor thymic cells stimulated with IL-2 represent a completely different T cell subset compared to IL-1-generated cells; these IL-2-stimulated cells express comparable levels of CD3, but also express substantial levels of CD2 and the TCR-gamma/delta, and a subset expresses CD8. These data suggest that these two TCR-alpha/beta and TCR-gamma/delta subsets of mature thymocytes use different cytokines and therefore possibly different stromal interactions to initiate differentiation.