bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of in vivo immune response by tumor necrosis factor.
Authors: Ghiara P , Boraschi D , Nencioni L , Ghezzi P , Tagliabue A 
Published: December 2022

Abstract
Interleukin 1 (IL-1) has been shown to regulate several immunologic functions. Since tumor necrosis factor (TNF) shares many biologic properties with IL-1, we have investigated here the role of TNF in the modulation of the immune response. We have thus tested low doses of human recombinant TNF-alpha (hu rTNF-alpha) for its capacity to enhance the in vivo antibody responses evaluated at the cellular level in the hemolytic plaque assay. It was found that hu rTNF-alpha, like human IL-1 beta, is able to enhance the immune response to a T cell-dependent antigen (sheep red blood cells). Interestingly, at variance with human recombinant IL-1 beta, hu rTNF-alpha was not able to enhance the in vivo antibody response to a T cell-independent antigen (type III pneumococcal polysaccharide). These results suggest that low levels of TNF may have a role in the modulation of the immune response in vivo and shed new light on the biologic significance of this mediator.
Developmental sequence of T200 antigen modifications in murine T cells.
Authors: Lefrancois L , Goodman T 
Published: December 2022

Abstract
The T200 glycoproteins of T cells were analyzed at different stages of T cell development. Immunoprecipitation and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that Lyt-2-L3T4-, and Lyt-2+L3T4+ thymocytes had similar T200 proteins, whereas Lyt-2+L3T4- and Lyt-2-L3T4+ thymocytes expressed a distinct set of T200 molecules. This result indicated a molecular switch in regulation of T200 protein expression upon differentiation of thymocytes to mature phenotype T cells. Further modifications were evident when the T200 proteins of peripheral T cell subsets were examined. In particular L3T4+ T cells expressed T200 proteins of m.w. 220,000, 200,000, and 175,000, whereas Lyt-2+ lymph node T cells expressed an additional T200 protein of m.w. 235,000. Antigenic differences in the T200 glyco-proteins of peripheral L3T4+ and Lyt-2+ T cells were also detected. The anti-B220 monoclonal antibody, 14.8, reacted with lymph node Lyt-2+ T cells but did not react with lymph node L3T4+T cells or with Lyt-2+L3T4- thymocytes. This finding demonstrated a lineage-specific modification of the T200 protein of Lyt-2+ T cells that occurred after exit of these cells from the thymus into peripheral lymphoid organs. This modification apparently occurred on the m.w. 235,000 and 220,000 proteins since these species were precipitated by 14.8, whereas the others were not. In vitro growth and activation also resulted in further T200 antigen alterations. The monoclonal antibody, RA3, which reacts with the B220 antigen of B cells but, unlike 14.8, does not react with any peripheral T cells, showed significant reactivity with Lyt-2+ cytotoxic T cell (CTL) clones but not with L3T4+ T helper cell clones. CTL clones were also 14.8+ but T helper cell clones were not. Immunoprecipitation by 14.8 and RA3 of T200 proteins from CTL clones yielded a single protein of m.w. 240,000 that co-migrated with the B cell form of T200. Overall, the results indicate the presence of developmentally regulated mechanisms that control T200 glycoprotein expression during T cell differentiation in the thymus and in peripheral lymphoid organs.
Modulation of two distinct galactosyltransferase activities in populations of mouse peritoneal macrophages.
Authors: Sheares B T , Mercurio A M 
Published: December 2022

Abstract
We have examined two galactosyltransferase activities in membrane preparations obtained from resident macrophages, from resident macrophages maintained in culture for 24 hr, and from thioglycollate (TG)-elicited macrophages. Transfer of galactose from uridine diphosphate (UDP)-galactose to N-acetylglucosamine is 2.6 times higher in membranes prepared from TG macrophages (107 +/- 5.5 nmol/hr/mg) than in membranes prepared from resident macrophages (41 +/- 2.0 nmol/hr/mg). Membranes obtained from resident macrophages cultured for 24 hr exhibit a 2.5 times higher activity (102 +/- 4.4 nmol/hr/mg) than membranes from resident cells plated for 4 hr. Transferase activity in membranes derived from TG macrophages is not significantly affected by overnight culture. The transferase reaction product, isolated on Bio-Gel P-4 and analyzed by galactosidase treatments, was identified as galactosyl-beta 1, 4-N-acetylglucosamine. The enzyme, therefore, is UDP-galactose:2-acetamido-2-deoxy-D-glucose 4 beta-galactosyltransferase. This is supported by the fact that this galactosyltransferase activity is specifically inhibited by high concentrations of N-acetylglucosamine (200 mM). We have also examined the transfer of galactose to N-acetyllactosamine. Membranes from TG-elicited macrophages contain a UDP-galactose:galactosyl-beta 1, 4-N-acetylglucosamine 3 alpha-galactosyltransferase which synthesizes the trisaccharide, galactosyl-alpha 1, 3-galactosyl-beta 1,4-N-acetylglucosamine. This product was identified by gel filtration chromatography, high performance liquid chromatography, and galactosidase digestions. This alpha-galactosyltransferase activity was not detected in membranes prepared from resident macrophages. These results indicate that glycosyltransferase activities are modulated in populations of mouse macrophages, and that these changes correlate with changes in cell surface lactosaminoglycans reported previously.
Inhibition of murine lymphocyte proliferation by the B subunit of cholera toxin.
Authors: Woogen S D , Ealding W , Elson C O 
Published: December 2022

Abstract
Cholera toxin is known to inhibit lymphocyte activation in vitro, an effect attributed to its ability to activate adenylate cyclase and increase intracellular cyclic adenosine monophosphate. In these studies the effects of both cholera toxin (CT) and its purified binding subunit (CT-B) on lymphocyte proliferation in vitro was examined, using a variety of cell activators. We found that both CT and CT-B inhibited mitogen- and antigen-induced T cell proliferation and anti-IgM-induced B cell proliferation in a dose-dependent manner. However, only CT-inhibited lipopolysaccharide-induced B cell proliferation. Neither CT nor CT-B inhibited antigen uptake and presentation by macrophages. The CT-B preparation used was shown not to activate lymphocyte adenylate cyclase, although CT itself was a strong activator of this enzyme. Both molecules had to bind to the lymphocyte surface in order to inhibit. The time course of inhibition of both CT and CT-B was similar in that either could be added up to 24 hr after culture initiation and still inhibit substantially. The addition of excess human recombinant interleukin 2 to the cultures did not affect the inhibition by CT, and had only a partial affect on inhibition by CT-B. Similarly, CT was able to substantially inhibit recombinant interleukin 2-dependent T lymphoblast proliferation, whereas CT-B had only a small inhibitory effect. Inhibition was not major histocompatibility complex-restricted. We conclude that the binding of CT or CT-B to the lymphocyte surface membrane interferes in some way with the activation mechanism leading to proliferation. The inhibition mediated by CT-B does not involve the stimulation of intracellular adenylate cyclase. CT appears to inhibit both by binding via its B subunit and by activation of adenylate cyclase via its A subunit.
How immunoglobulin V kappa genes rearrange.
Authors: Shapiro M A , Weigert M 
Published: December 2022

Abstract
Recombination at the immunoglobulin kappa light chain locus creates a complete variable region gene and its reciprocal product. The results presented here show that reciprocal products may be substrates for secondary recombination and that at least one V kappa group rearranges by inversion.
Immunologic competence of B cells subjected to constitutive c-myc oncogene expression in immunoglobulin heavy chain enhancer myc transgenic mice.
Authors: Vaux D L , Adams J M , Alexander W S , Pike B L 
Published: December 2022

Abstract
B cell activation is associated with a marked transient rise in expression of the c-myc proto-onco-gene. A unique opportunity to examine the effects of constitutive c-myc expression upon B cell function is provided by transgenic mice in which the c-myc oncogene is regulated by the enhancer (E mu) from the immunoglobulin locus (E mu-myc mice). We have examined the immunologic competence of B cells from E mu-myc mice both in vitro and in vivo. Upon stimulation, many E mu-myc B cells can proliferate to form clones most of which contain antibody-forming cells. However, the frequency of responsive B cells from E mu-myc donors is only about 30% that of B cells from normal littermates. Thus, enforced myc expression is not sufficient to block the differentiation of all B cells, but a much larger fraction of the immunoglobulin-bearing cells from E mu-myc mice are incompetent. Upon immunization, E mu-myc mice mounted specific antibody responses, although some responses were delayed. Isotype switching can occur, since we observed hemolytic plaques of both IgM and IgG type and detected specific antibody of both classes in the serum. Moreover, the serum from nonimmunized E mu-myc mice contained normal levels of both IgM and IgG. Thus constitutive expression of the c-myc gene appears to retard B cell differentiation, but does not grossly impair immunologic function in the intact animal.
Characteristics of two idiotypic subfamilies of murine anti-p-azobenzenearsonate antibodies.
Authors: Robbins P F , Nisonoff A 
Published: December 2022

Abstract
A family of antibodies bearing a common or cross-reactive idiotype, termed CRIC, predominates in the response of most BALB/c mice to the p-azobenzenearsonate (Ar) hapten, but represents a minor component of the anti-Ar response of most A/J mice. Previous results have suggested that the VH region of CRIC is encoded by two different germ-line genes in both strains. We have determined extensive mRNA sequences for VH and VL, developed specific idiotypic reagents and measured affinities for two subfamilies of CRIC, designated CRIC1 and CRIC2. Both were found to be minor components of A/J anti-Ar antibodies, and CRIC1, but not CRIC2, is a major component of the BALB/c response. The two subfamilies utilize different VH germ-line genes but the same, or nearly identical V kappa genes. The VH nucleotide sequences of CRIC1 and CRIC2 exhibit approximately 90% homology. The D regions of both families are short (one or two amino acid residues) and some can be accounted for on the basis of known JH sequences alone. Affinity differences may account for the dominance of CRIA over CRIC1 and CRIC2 in A/J mice, but results obtained with allotype-congenic mice indicate that background (non-V region) genes are also important in controlling levels of expression of the CRIC1 idiotype. Our data suggest that the A/J germline VH gene that gives rise to the CRIC2 family of antibodies may be identical with a previously sequenced BALB/c germ-line VH gene. On the basis of these and earlier data it is suggested that extensive differences between inbred strains of mice in their complements of VH genes do not result from the accumulation of many mutations in these genes. An alternative possibility is that the differences arise from deletions and/or duplications of VH genes.
Major histocompatibility complex-unrestricted cytolytic activity of human T cells. Analysis of precursor frequency and effector phenotype.
Authors: Patel S S , Thiele D L , Lipsky P E 
Published: December 2022

Abstract
The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. These conditions were shown to expand a mean of 96% of cells cultured. All of the 198 clones generated by this method were T cells (CD2+, CD3+, CD4+ or CD2+, CD3+, CD8+) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. In addition, the activity was not inhibited by monoclonal antibodies directed against class I or class II nonpolymorphic MHC determinants. Killing, however, was inhibited by soluble monoclonal antibodies against the CD3 complex. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur or K562 was not mediated by a soluble factor secreted by the clones. Some of the clones retained their cytotoxic activity when grown in rIL-2 alone for 4 to 6 wk, whereas others exhibited markedly diminished cytotoxicity after maintenance in this manner. Clones that exhibited diminished or no cytotoxic activity after prolonged maintenance in rIL-2 could be induced to kill by stimulation with immobilized but not soluble monoclonal antibodies to CD3 in the absence of lectin. All of the clones examined expressed NKH1 and CD11b but none were CD16 positive. The degree of cytotoxicity of resting or activated clones could not be correlated with expression of these markers. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype.
Dissociation of alloantigen recognition from self major histocompatibility complex-restricted recognition of cytolytic T lymphocytes by monoclonal antireceptor antibodies.
Authors: Kanagawa O , Nagasawa R 
Published: December 2022

Abstract
Two monoclonal antibodies (mAb) directed to the dual reactive cytolytic T lymphocyte clone OH8 (Db + H-Y and H-2d) were established. Analysis by cell surface staining and immunoprecipitation of radiolabeled surface molecules of OH8 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that both mAb recognized an identical heterodimeric, clonotypic structure on OH8 cells, i.e., T cell receptor. However, although the MR3-2 mAb inhibited the lysis of either Db + H-Y or H-2d targets by OH8, the MR3-6 mAb inhibited the lysis of H-2d target cells, but not that of Db + H-Y target cells. Modulation of T cell receptor by either MR3-2 or MR3-6 mAb rendered the OH8 cytolytic T lymphocyte incapable of killing both Db + H-Y and H-2d target cells. These findings suggest that different epitopes of OH8 T cell receptor were involved for the recognition of self + antigen and alloantigen.
Characterization and epitope mapping of a human monoclonal antibody reactive with the envelope glycoprotein of human immunodeficiency virus.
Authors: Banapour B , Rosenthal K , Rabin L , Sharma V , Young L , Fernandez J , Engleman E , McGrath M , Reyes G , Lifson J 
Published: December 2022

Abstract
A human monoclonal antibody (IgG2, lambda), 1B8.env, was produced, reactive with the envelope glycoprotein of human immunodeficiency virus (HIV). The antibody specifically stains cells infected with HIV, as assessed by indirect immunofluorescence analysis and reacts with determinants displayed on the surface of infected cells. In Western blot analysis, the antibody reacts with bands of 160 and 41 kD, consistent with the precursor and transmembrane forms of the HIV envelope glycoprotein. The antibody also reacts specifically in immunofluorescence and Western blot analysis with cells infected with the recombinant vaccinia virus VSC-25, which contains the envelope gene of HIV. With the lambda gt11 expression vector, the epitope recognized by 1B8.env was mapped to a region of 11 amino acids in the coding region of gp41. This domain is highly conserved between several otherwise highly variable HIV isolates. In addition, this epitope appears to be recognized by the vast majority of HIV seropositive individuals. Although antibody IB8.env does not neutralize HIV virion infectivity or virally mediated cell fusion, the results presented here demonstrate the feasibility of generating and characterizing human monoclonal antibodies to HIV with these techniques. Additional antibodies produced in this manner will help to further characterize the humoral response to HIV infection, define biologically significant determinants on HIV proteins, and may be useful in clinical applications.
T-cell-derived IgE-binding factors. II. Purification and characterization of IgE-binding factors produced by human T cell leukemia/lymphoma virus-1-transformed T lymphocytes.
Authors: Sarfati M , Nutman T B , Suter U , Hofstetter H , Delespesse G 
Published: December 2022

Abstract
We previously described human T cell leukemia/lymphoma virus-1-transformed T cell clones expressing surface molecules binding to monoclonal antibodies against lymphocyte Fc epsilon receptor (Fc epsilon R) and releasing soluble factors binding to both IgE and to monoclonal antibody to lymphocyte Fc epsilon R. In this study, one such clone (HE1-11) was tested for the presence of mRNA hybridizing with a cDNA probe coding for Fc epsilon R on B cells. Northern blot analysis revealed the presence of the same 1.7 kb Fc epsilon R mRNA in HE1-11 and in RPMI 8866 cells as well as in the macrophage cell line U937, expressing Fc epsilon R. The IgE binding factors (BF) released by HE1-11 cells appeared to be identical to those released by RPMI 8866 cells as shown by 1) one- and two-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis analysis and 2) tryptic peptides analysis. IgE-BF are microheterogeneous containing molecules with molecular mass of 25 to 27 kDa and with isoelectric point ranging from 4.5 to 5. Some preparations further contained 16-kDa fragments of IgE-BF. These findings suggest that the gene coding for both Fc epsilon R and IgE-BF may also be expressed on some human T cells.
Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells.
Authors: Baumann H , Richards C , Gauldie J 
Published: December 2022

Abstract
Human hepatoma (HepG2) cells respond to unfractionated conditioned media of human squamous carcinoma (COLO-16) cells and lipopolysaccharide-stimulated human peripheral blood monocytes by increasing the synthesis of alpha 1-acid glycoprotein, haptoglobin, complement C3, alpha 1-antichymotrypsin, alpha 1-antitrypsin, and fibrinogen, while decreasing the synthesis of albumin. The regulation of the acute phase proteins is mediated by hepatocyte-stimulating factors (HSF) and interleukin 1 (IL-1) present in the conditioned medium. Purified HSF-I from COLO-16 cells stimulates preferentially alpha 1-acid glycoprotein synthesis, whereas COLO-HSF-II stimulates preferentially the synthesis of haptoglobin, fibrinogen, and alpha 1-antitrypsin. HSF from monocytes, which has been identified as interferon-beta 2 (B cell stimulating factor-2), displayed the same activity as COLO-HSF-II. Dexamethasone alone had no effect on acute phase plasma protein synthesis but enhanced the response to various HSF severalfold. IL-1 had a relatively low stimulatory activity on the synthesis of alpha 1-acid glycoprotein, haptoglobin, and alpha 1-antichymotrypsin but strongly reduced the basal expression of fibrinogen. The only synergistic action between IL-1 and HSF (or interferon-beta 2) was noted for the synthesis of alpha 1-acid glycoprotein. Tumor necrosis factor active on other hepatic cells failed to modulate significantly the expression of any plasma proteins in HepG2 cells. These studies showed that for an optimal HepG2-cell response a combination of HSF (or interferon-beta 2), IL-1, and dexamethasone is needed. This finding might indicate the identity of some of those hormones involved in regulation of the hepatic acute phase response in vivo.
Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cells.
Authors: Knudsen P J , Dinarello C A , Strom T B 
Published: December 2022

Abstract
We investigated effects of corticosteroids on interleukin 1 (IL-1) production in monocyte-like tumor cell line, U937. Release of IL-1 activity by bacterial toxin-stimulated cells was completely blocked by 10 nM dexamethasone (Dex). We examined the question whether corticosteroids suppress IL-1 production by blocking transcription of IL-1 mRNA, or by blocking IL-1 synthesis at a post-transcriptional step. Northern blot hybridization analysis indicated that Dex, 10 nM, completely blocked accumulation of IL-1 beta-encoding mRNA in U937 cells. Dex-mediated inhibition of IL-1 release appeared to be glucocorticoid receptor-mediated and was abrogated by progesterone. In addition, Dex at high concentrations could inhibit post-transcriptional synthesis of IL-1 by prestimulated U937 cells. Although Dex, 500 nM, did not change IL-1 mRNA levels in prestimulated cells, it completely blocked IL-1 release and induced a transient increase in cellular cyclic adenosine 3',5'-monophosphate (cAMP) levels. Dex-mediated inhibition of IL-1 release in prestimulated cells is likely to occur via increased levels of cAMP, which have been shown to block post-transcriptional IL-1 synthesis. Our results indicate that glucocorticoids suppress IL-1 synthesis by two distinct mechanisms, blocking transcription of IL-1 mRNA during monocyte activation, and blocking post-transcriptional IL-1 synthesis via cAMP.
Contributions of immunoglobulin heavy and light chains to antibody specificity for lysozyme and two haptens.
Authors: Smith-Gill S J , Hamel P A , Lovoie T B , Dorrington K J 
Published: December 2022

Abstract
Chain recombination experiments with a set of structurally and/or functionally related antibodies were performed to assess the role of the heavy (H) and light (L) chains in determining antigen specificity. The results demonstrated that specificity for hen egg white lysozyme vs two haptens (dinitrophenyl or galactan) is H chain determined and for one set of proteins could be attributed specifically to the H3 region. In contrast to hapten vs lysozyme specificity, when reassociated molecules derived from structurally unrelated antibodies that bound nonoverlapping epitopes on lysozyme were tested, localization of binding to a particular epitope on lysozyme could be predominated by either H or L chains. Furthermore, in some cases, unique specificities distinct from those of either parental antibody were formed. Replacement of the native L chain with an isotypically homologous L chain was more likely to restore high affinity protein binding than was replacement of a less related L chain. When isotypically homologous L chains were compared in association with the same H chain, fine specificity profiles were sensitive to substitutions in as few as two residues that could be attributed to somatic mutation. These results demonstrate that both affinity and specificity derive from very subtle interactions between H and L chains and provide examples of how VH assembly, VL-VH pairing, and somatic mutation could contribute to development and maturation of the specificity repertoire.