bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier-induced epitopic suppression, a major issue for future synthetic vaccines.
Authors: Schutze M P , Leclerc C , Jolivet M , Audibert F , Chedid L 
Published: December 2022

Abstract
Synthetic antigens have been shown, in experimental models, to induce protective immunity against a variety of pathogens. These studies have demonstrated that, due to their low immunogenicity, these synthetic antigens required conjugation to carrier molecules. Therefore, the choice of appropriate carriers for human immunization by future synthetic vaccines is a major issue. Tetanus toxoid is generally considered to be an effective potential carrier devoid of side-effects. However, the present study performed in mice with two synthetic vaccine models demonstrates that the immune response against the synthetic epitopes conjugated to tetanus toxoid can be suppressed by pre-existing immunity against this same carrier. Because most humans have been exposed to this antigen, this effect may have important implications for the development of synthetic vaccines.
Mode of in vitro augmentation of natural killer cell activity by recombinant human interleukin 2: a comparative study of Leu-11+ and Leu-11- cell populations in cord blood and adult peripheral blood.
Authors: Seki H , Ueno Y , Taga K , Matsuda A , Miyawaki T , Taniguchi N 
Published: December 2022

Abstract
Human newborn natural killer (NK) cell activity against K562 target cells was observed to be low compared with adult controls. Although Leu-7 (HNK-1)+ cells were negligible in cord blood, the proportions of Leu-11+ cells were equal to those of adult peripheral blood. Leu-11+ cells sorted from cord blood lymphocytes, as well as from adult lymphocytes exhibited the morphology of granular lymphocytes. In this study, we have investigated the phenotypic characterization of recombinant interleukin 2 (rIL 2)-induced cytotoxic lymphocytes against K562 cells by using anti-Leu-11 monoclonal antibody. Spontaneous cytotoxicity of lymphocytes was restricted to Leu-11+ cells in cord blood, as well as in adult blood, but this activity was low in cord blood Leu-11+ cells as compared with that of adult ones. NK cell activity of adult Leu-11+ cells could not be additionally enhanced after an 18-hr incubation with rIL 2(25 U/ml), whereas rIL 2 could potentiate the cytotoxicity of cord blood Leu-11+ cells approximately to the adult levels. It should be noted that cytotoxic activity of both Leu-11- cells from cord blood and adult blood that had no basal NK cells activity could be significantly potentiated by rIL 2. On the other hand, lymphokine-activated killer cells cytotoxic for HL-60 cell line could not be generated, and no proliferation of the lymphocytes was detected after an 18-hr incubation with rIL 2. It was shown that rIL 2 could not enhance the ability to bind to target cells in Leu-11+ and Leu-11- cells by means of a single cell conjugate assay, but the rate of target lysis of Leu-11+ cells from cord blood was significantly enhanced by rIL 2. These results suggested that rIL 2-induced cytotoxic effector cells were heterogeneous, and rIL 2 might potentiate the cytotoxicity of functionally immature NK cells or NK precursor cells.
Competition between antigen and anti-idiotypes for rheumatoid factors.
Authors: Nelson J L , Nardella F A , Mannik M 
Published: December 2022

Abstract
Many idiotypic determinants on antibody molecules are thought to be located at the antigen binding site, and therefore the interaction between idiotype (Id) and anti-idiotype (anti-Id) is expected to be inhibited by the antigen. We describe two IgG and one IgM rheumatoid factors whose interactions with their respective anti-Id could only be partially inhibited by very large amounts of antigen, i.e., normal IgG. The anti-Id, however, readily inhibited the binding of their respective rheumatoid factors to IgG. The differences in interaction energies resulted in failure of antigen to readily block the Id-anti-Id interaction, and did not mean that the Id was not at the antigen combining site. The association constants for the Id-anti-Id interactions varied from 1.3 to 14.8 X 10(7) M-1, whereas the strength of the rheumatoid factor antigen bond is on the order of 10(5) M-1 for interaction with monomeric IgG. In addition, the anti-Id were able to remove rheumatoid factors that were bound to solid phase IgG, indicating that anti-Id have the potential for disrupting the immune complexes formed by antigen and antibody.
Specific and shared idiotypes found on hybridoma anti-DNA autoantibodies derived from rheumatoid arthritis and systemic lupus erythematosus patients.
Authors: Rauch J , Massicotte H , Tannenbaum H 
Published: December 2022

Abstract
The idiotype determinants found on hybridoma anti-DNA autoantibodies produced from the fusion of peripheral blood lymphocytes from 13 systemic lupus erythematosus (SLE) and five rheumatoid arthritis (RA) patients with the GM 4672 human lymphoblastoid line were analyzed. A total of 47 SLE and 21 RA hybridomas were studied, of which 26 SLE and 10 RA produced anti-DNA autoantibodies. Rabbit antisera, raised to six of the SLE hybridoma anti-DNA IgM antibodies, were rendered idiotype specific by multiple absorptions on human IgM and IgG immunoabsorbent columns. In direct binding radioimmunoassays, all six anti-idiotype antisera reacted specifically with the anti-DNA antibody used as immunogen. In competition studies, five anti-idiotype antisera were able to inhibit the binding of their homologous idiotype to DNA-coated tubes. In addition, DNA and polynucleotides inhibited the binding of the five idiotypes to anti-idiotype-coated tubes, suggesting that these anti-idiotypes react with idiotype determinants located within the antigen-combining sites of the anti-DNA antibody molecules. Shared idiotypes were detected among the 68 hybridoma antibodies by direct binding studies on anti-idiotype-coated tubes. Our results revealed that 58% (21/36) of the anti-DNA antibodies and 16% (5/32) of the non-DNA-binding antibodies reacted with at least one anti-idiotype serum. Five anti-idiotype antisera reacted only with hybridoma anti-DNA antibodies from SLE patients. The other anti-idiotype antiserum reacted with both SLE- and RA-derived hybridoma anti-DNA and non-DNA-binding antibodies. These studies indicate that some anti-idiotype antisera may detect specific idiotypes found only on SLE-derived anti-DNA auto-antibodies, whereas other antisera detect shared idiotypes found on both RA and SLE DNA-binding and non-DNA-binding antibodies.
Functional analysis of T cell subsets from mice bearing the lpr gene.
Authors: Davignon J L , Budd R C , Ceredig R , Piguet P F , MacDonald H R , Cerottini J C , Vassalli P , Izui S 
Published: December 2022

Abstract
The autosomal recessive lpr (lymphoproliferation) gene is responsible for a thymus-dependent massive lymphoproliferation associated with the development of lupus-like autoimmune disease. Phenotypic analysis of adult lpr/lpr lymph nodes has demonstrated accumulation of a dull Lyt-1+, Thy-1+ population that expresses neither Lyt-2 nor L3T4 antigens. With the use of a depletion method based on complement-mediated lysis with an anti-Lyt-2 monoclonal antibody (31 M) and a new anti-L3T4 monoclonal antibody (RL 172.4), we have purified the Lyt-2- L3T4- subset from lymph nodes or spleens of C57BL/6-lpr/lpr mice and determined whether they are immunologically functional in vitro. Production of neither interleukin 2 nor interferon-gamma was detected by the double-negative subset after stimulation with concanavalin A and/or phorbol myristate acetate. The frequencies of allospecific cytotoxic T lymphocyte (CTL) precursors and lectin-induced antigen-nonspecific CTL precursors were diminished to almost undetectable levels, whereas the Lyt-2+ population from lpr/lpr mice had CTL-precursor frequencies comparable with that of +/+ mice. These results show that the major cell subset of adult lpr/lpr lymph nodes or spleens is composed of lymphocytes with markedly limited potential for lymphokine production or antigenic stimulation.
Two defects in old New Zealand Black mice are involved in the loss of low-dose paralysis to type III pneumococcal polysaccharide.
Authors: McCoy K L , Baker P J , Stashak P W , Chused T M 
Published: December 2022

Abstract
Treatment of normal mice with a subimmunogenic dose of type III pneumococcal polysaccharide (SSS-III) results in the development of an antigen-specific state of unresponsiveness termed low-dose paralysis. This unresponsiveness is mediated by T suppressor cells and can be transferred by Lyt-2+ T cells, but not by L3T4+ T cells, obtained 18 hr after priming. As autoimmune New Zealand Black (NZB) mice age, there is a progressive decrease in low-dose paralysis to SSS-III. The defect in older NZB mice resulting in decreased suppressive activity was investigated by transferring primed Lyt-2+ T cells from young into old mice, and vice versa. Enlarged Lyt-2+ T cells from old NZB mice could not suppress the SSS-III response of young recipients. However, Lyt-2+ T cells of normal cell size were efficient in inhibiting the antibody response upon transfer. Primed Lyt-2+ T cells from young NZB mice did not affect the response of old recipients, but effectively suppressed the response of young mice. These results suggest that there are two defects involved in the decline of low-dose paralysis to SSS-III in aging NZB mice: Enlarged Lyt-2+ T cells may lose their ability to function as mediators of suppression; and B cells may become resistant to T cell-mediated suppression.
Interaction of interleukin 2 with cells: quantitative analysis of effects.
Authors: Hooton J W , Gibbs C , Paetkau V 
Published: December 2022

Abstract
The response of T lymphocytes to interleukin 2 (IL 2) is accurately described by a four-parameter logistic function. Both data generated by a theoretical model of IL 2-driven proliferation and experimental data conformed to this function for all doses of IL 2. Assays measuring either the rate of DNA synthesis or cellular metabolism were well described. The variance of response was not constant but increased in a predictable way. Weighting was therefore included in deriving a nonlinear curve-fitting program. The effects on response of cell density, time, and the T lymphocyte line used were examined. Assays gave reproducible estimates of potency when test preparations were compared with a standard preparation, but not otherwise. A model for IL 2 proliferation was derived on the basis of the two-state model of the cell cycle, with cells leaving a quiescent state randomly and then traversing the other stages of the cell cycle in a determinate way.
Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta.
Authors: Nedwin G E , Svedersky L P , Bringman T S , Palladino M A , Goeddel D V 
Published: December 2022

Abstract
Human peripheral blood mononuclear cells (PBMC) were induced by recombinant interleukin 2 and mitogens to secrete two distinct cytotoxic polypeptides, tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta), previously called lymphotoxin. Treatment of PBMC with recombinant human interleukin 2 (rIL 2) or mitogens in combination with recombinant human interferon-gamma (rIFN-gamma) resulted in augmented production of both TNF-alpha and TNF-beta. rIFN-gamma alone had no effect on production of either cytotoxic polypeptide. TNF-alpha was produced within 2 to 3 hr after induction and was the major cytotoxin produced by PBMC during the first 48 hr of culture, after which time TNF-beta became the predominant species. TNF-beta was first secreted into the media after 8 hr of induction. Enhanced levels of both TNF-alpha and TNF-beta were seen when the PBMC were separated into adherent and nonadherent cells. Both TNF-alpha and TNF-beta were induced in different tumor cell lines of hematopoietic origin. The results demonstrate that the production of TNF-alpha and TNF-beta can be enhanced by two lymphokines, IL 2 and IFN-gamma.
Partial purification of murine B cell stimulatory factor (BSF)-1.
Authors: Ohara J , Lahet S , Inman J , Paul W E 
Published: December 2022

Abstract
BSF-1 was partially purified from serum-free culture supernatants of cells of the EL-4 thymoma line, which had been induced 48 hr earlier with 4 beta-phorbol-12 beta-myristate-12 alpha-acetate (PMA). BSF-1 in 10-liter batches was adsorbed onto and eluted from trimethylsilyl-controlled pore glass beads (TMS-CpG) and then subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). The recovery of BSF-1 activity by TMS-CpG and RP-HPLC ranged from 52 to 55% and 187 to 227%, respectively. The specific activity in units per milligram of protein of partially purified BSF-1 was approximately 2600 times higher than that of the culture supernatant protein. The partially purified BSF-1 had a single isoelectric point of 6.3 and an apparent m.w. between 18,000 and 21,700 when analyzed by isoelectric focusing and gel filtration-HPLC, respectively. The ability to prepare large amounts of partially purified BSF-1 by a rapid and efficient procedure should be of great help in both biochemical and immunologic studies of this lymphokine.
A naturally occurring polyclonal B cell activator of normal and autoantibody responses.
Authors: Atkinson M J , Bell D A , Singhal S K 
Published: December 2022

Abstract
Previous studies from this laboratory have demonstrated the presence of a suppressor molecule in B/W spleen cultures. Now we present evidence suggesting the existence of a polyclonal B cell activator (sPBA) spontaneously released by B/W splenocytes. Large sPBA (120,000 to 160,000 daltons) was separable from splenic inhibitory factor(s) (less than 10,000 daltons) by ultrafiltration. Reconstitution experiments demonstrated these two molecules had antagonistic effects on splenocyte mitotic events. sPBA is directly mitogenic for T cell-depleted, B cell-enriched cultures. Furthermore, sPBA augments antibody responses in the presence of antigen, or stimulates antibody responses in the absence of antigen. sPBA appears to stimulate IgG as well as IgM antibody production. sPBA stimulates significant in vivo anti-ssDNA responses in preautoimmune B/W but not DBA mice. Physiochemical studies suggest sPBA is a DNA protein complex. sPBA activity is completely lost by heating to 56 degrees C for 30 min. sPBA activity is precipitated at pH 7.8 to 8.0. Furthermore, sPBA preparations do not display significant endotoxin levels or IL 1 and IL 2 activity.
Role of N-acetyl-D-galactosamine residue on B151K12-derived T cell-replacing factor (B151-TRF) molecule in B cell-receptor binding and -stimulating activity.
Authors: Takahama Y , Ono S , Hara Y , Hayashi S , Dobashi K , Hamaoka T 
Published: December 2022

Abstract
The role of sugar moiety on T cell-replacing factor molecule derived from a monoclonal T cell hybridoma B151K12 (B151-TRF) was analyzed with respect to the interaction with receptor on B cells. The induction of B cell differentiation into Ig-secreting cells by B151-TRF was specifically inhibited by addition of N-acetyl-D-galactosamine (GalNAc) to culture. Such inhibition appeared to be attributed to the interference of GalNAc in the interaction of TRF with its receptor, because absorption of TRF activity with B cells was notably inhibited by the presence of GalNAc. To substantiate this point further, we established binding assay of B151-TRF molecule to the receptor on B cells by using 125I-labeled TRF fraction enriched by reversed-phase high-performance liquid chromatography and gel filtration. The results revealed that the binding of 125I-TRF molecule to the B cells was almost completely blocked by GalNAc. Moreover, the existence of GalNAc residue(s) on B151-TRF molecule was evidenced by the facts that 1) the TRF activity was eluted from lectin gels with specificity for GalNAc as revealed by the functional assay, and 2) the 125I-TRF molecule specifically bound to such lectin gels. Thus, the GalNAc residue(s) on B151-TRF molecule plays an important role in binding of TRF molecule to the receptor and in the stimulation of B cells. The molecular properties of B cell-stimulatory B151-TRF and its mode of interaction with corresponding receptor on B cells were discussed in the context of B151-TRF as a glycosylated lymphokine molecule and B151-TRF receptor as a carbohydrate-binding protein (animal lectin).
Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice.
Authors: Noguchi M , Ogasawara M , Iwabuchi K , Osgasawara K , Ishihara T , Good R A , Morikawa K , Onoé K 
Published: December 2022

Abstract
We have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, we analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that provided by the thymuses of the recipient mice.
Purification and partial sequence of human osteoclast-activating factor: identity with interleukin 1 beta.
Authors: Dewhirst F E , Stashenko P P , Mole J E , Tsurumachi T 
Published: December 2022

Abstract
The lymphokine osteoclast-activating factor (OAF) was purified to homogeneity. OAF was produced by human peripheral blood mononuclear cells stimulated with concanavalin A and phorbol myristate acetate under serum-free culture conditions. OAF was purified by sequential gel filtration, ion-exchange, and reverse-phase HPLC by following bone resorptive activity. Homogeneity was indicated by the criteria of a single 17,800-dalton band on silver-stained polyacrylamide gels, a single pI 6.8 band on isoelectric focusing, and a single aminoterminal sequence. Purified OAF stimulated half-maximal release of calcium from fetal rat long bones at a concentration of approximately 0.66 ng/ml. The amino-terminal sequence of OAF was determined and found to be identical to that of interleukin 1 beta. Homogeneous OAF possessed an activity of 8.2 X 10(6) U/mg in the thymocyte proliferation assay. Because the m.w., isoelectric point, amino-terminal sequence, and specific activity in the thymocyte proliferation assay are the same for homogeneous OAF and interleukin 1 beta, we conclude that they are the same molecule, and that interleukin 1 beta is the major protein with OAF activity produced by lectin-stimulated peripheral blood mononuclear cells.
Antibody-independent activation of C1, the first component of complement, by cardiolipin.
Authors: Kovacsovics T , Tschopp J , Kress A , Isliker H 
Published: December 2022

Abstract
Lipid vesicles containing phospholipids known to be present in substantial amounts in mitochondrial membranes were tested for their capacity to activate C1. Among them, only cardiolipin (CL) was highly efficient in C1 activation; no such effect was observed with phosphatidylcholine, phosphatidylethanolamine, or phosphatidylinositol. CL was shown to bind specifically C1q, because only unlabeled C1q competed with 125I-C1q for binding to CL. The requirement for C1q was confirmed by the finding that only fully reconstituted macromolecular C1, containing C1q, was activated by CL. The specificity of CL-induced activation of C1 was also demonstrated by introducing adriamycin, an agent known to interact with CL. Whereas adriamycin did not decrease C1 activation induced by immune complexes, it abrogated C1 activation by CL. The latter was shown to be a strong nonimmune activator of C1, because C1-INH did not inhibit CL-induced activation. When the concentration of CL in vesicles was decreased in the presence of phosphatidylcholine, C1 activation was detected only above a critical level of 35 mol% CL, compatible with a minimal density or clustering of CL molecules in the plane of the membrane. Moreover, C1 activation by CL was modulated by the addition of cholesterol. The threshold of CL required for C1 activation was lowered by the incorporation of more than 35 mol% cholesterol into the vesicles. These results show that CL incorporated into liposomes can be a potent nonimmune activator of C1. The negatively charged phosphate groups in CL are likely candidates for Clq-binding.
Enhancement by cyclic AMP of antibody-induced suppression of the fourth component of complement.
Authors: Goldman M B , Becker D S , O'Rourke K S , Goldman J N 
Published: December 2022

Abstract
Our laboratory has shown that short-term treatment in vivo or in vitro with monospecific antibody to individual complement components can have long-term effects on the production of those components. In vitro studies have focused on the fourth component of complement (C4) in a guinea pig model. Uniform splenic fragments have been used to mimic the in vivo microenvironment of the C4-producing macrophages. A 4-day exposure to anti-C4 antibody led to a reduction of secreted C4 for 1 to 2 wk and a reduction of intracellular C4 that persisted even longer. In an attempt to understand how short-term exposure to antibody can specifically and permanently disrupt the C4-producing cell, we have determined whether C4 suppression could be enhanced by components that modulate cellular functions through their role as secondary intracellular messengers. We found that compounds which elevated cellular levels of cAMP by any of three mechanisms all enhanced antibody-induced suppression of C4.