bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential stability of antigenic MHC class I-restricted synthetic peptides.
Authors: Widmann C , Maryanski J L , Romero P , Corradin G 
Published: December 2022

Abstract
Various synthetic peptides recognized as Ag by CTL in the context of MHC class I molecules were tested for stability in vitro and in vivo. Peptide inactivation in vitro was quantitated by titrating the amount of peptide required to sensitize target cells for lysis by specific CTL clones. The degree of inactivation after overnight incubation at 37 degrees C varied widely among a series of antigenic peptides. Some were nearly unaffected, whereas others lost activity by more than 100-fold or even 10,000-fold. However, no correlation was found between susceptibility to serum inactivation and antigenic potency as measured in short term cytolytic assays. No inactivation occurred at 4 degrees C, or at 37 degrees C in the absence of serum, under the conditions used. Serum inactivation most likely involved proteolysis because it could be inhibited by protease inhibitors. Moreover, presumed cleavage products of a radiolabeled susceptible peptide could be visualized by TLC. In vivo, the persistence of the antigenic activity of the injected peptides, either in extracellular fluids or on tumor target cells growing in an ascites form, correlated with the degree of stability found for the peptides in vitro. The differential stability of synthetic peptides may have important consequences for attempts to manipulate the development of an immune response in vivo.
Characterization of accessory cell costimulation of Th1 cytokine synthesis.
Authors: Williams I R , Unanue E R 
Published: December 2022

Abstract
We studied the capacity of macrophage and B cell lines to provide a costimulatory signal that enhances synthesis of IFN-gamma and IL-2 by mouse Th1 clones stimulated with suboptimal doses of immobilized anti-CD3 antibody. The J774 macrophage line and the CH27 B lymphoma line had the greatest costimulatory activity and routinely increased IL-2 production by 10-fold to 100-fold. Other macrophage and B cell lines had less activity and T cell lines were unable to costimulate. The J774 and CH27 lines did not costimulate IL-4 production by a Th2 clone and had only a small effect on IL-2 production by T cell hybridomas. The process of costimulation was fixation-sensitive, contact-dependent and did not involve stable cytokines present in the T cell/accessory cell conditioned media. Neutralizing antibodies for IL-1, IL-6, and TNF failed to inhibit costimulation. Antibodies to the LFA-1/ICAM-1 pair of adhesion molecules also failed to inhibit. Costimulation of IL-2 production by accessory cells was found to have a unidirectional species restriction: mouse accessory cells costimulated mouse and human IL-2-producing T cells, but human U937 cells induced with PMA were effective only for human T cells. The results indicate that accessory cells can significantly regulate Th1 effector function at the level of cytokine production.
IL-1, IL-4, and IFN-gamma differentially regulate cytokine production and cell surface molecule expression in cultured human thymic epithelial cells.
Authors: Galy A H , Spits H 
Published: December 2022

Abstract
We investigated the response of purified and cloned human thymic epithelial cells (TEC) to IL-1, IL-4, and IFN-gamma stimulation in vitro. IL-1 alpha strongly up-regulated the production of granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), IL-6, and IL-8, as measured by specific immunoenzymetric assays and by increased steady state mRNA levels. IL-4 or IFN-gamma did not induce these cytokines in TEC but in a sustained and dose-dependent manner down-regulated the IL-1-induced GM-CSF protein and mRNA levels. Only IFN-gamma, and not IL-4, suppressed the IL-1-induced G-CSF and IL-8 production, as shown at both the protein and mRNA levels. The inhibition was dose dependent, sustained for at least 96 h, and more pronounced for G-CSF than for IL-8. In contrast, both IL-4 and IFN-gamma enhanced the IL-1-induced IL-6 production. IL-4 and IFN-gamma had additive effects to increase IL-6 secretion and to more completely suppress the IL-1-induced GM-CSF. Analyses of cell surface molecules showed that intercellular adhesion molecule 1 (ICAM-1) expression on TEC was increased by IL-1 or IFN-gamma. IL-4 slightly down-regulated constitutive ICAM-1 levels but did not significantly modify the levels of expression induced by either IL-1 or IFN-gamma. MHC class II expression was induced by IFN-gamma but not by IL-1 or IL-4. The combination of IL-1 and IL-4 with IFN-gamma did not alter the levels of class II MHC Ag induced by IFN-gamma. In conclusion, TEC cytokine production and cell surface molecule expression are differentially regulated via a complex cytokine network. Our data suggest that developing T cells provide, in part, the signals controlling the function of their supporting stroma.
Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells.
Authors: Matsuda M , Masutani H , Nakamura H , Miyajima S , Yamauchi A , Yonehara S , Uchida A , Irimajiri K , Horiuchi A , Yodoi J 
Published: December 2022

Abstract
Adult T cell leukemia-derived factor (ADF) is a human homologue of thioredoxin with many biologic functions including IL-2R induction, growth promotion, thiol-dependent reducing activity, and radical scavenging activity. The regulatory effect of ADF on the cytotoxic activity of TNF was examined by using a human histiocytic lymphoma cell line, U937. When U937 cells were preincubated with recombinant ADF (rADF) (0.1-100 micrograms/ml) at 37 degrees C for 30 min, TNF-dependent cytotoxicity on U937 cells was markedly inhibited. This inhibitory effect was as high as 95% in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (rADF 100 micrograms/ml) and 85% in the 51Cr-releasing assay (rADF 10 micrograms/ml). After pretreatment of U937 cells with IFN-gamma to augment the sensitivity to TNF, an inhibitory effect of rADF was also found. When U937 cells were washed after preincubation with rADF, resistance to TNF-dependent cytotoxicity was still observed, indicating that rADF inhibited the sensitivity of U937 to TNF-dependent cytotoxicity rather than modifying TNF molecules. Scatchard analysis of TNF receptors on U937 cells using 125I-TNF showed that rADF modulated neither the density nor the affinity of the cell membrane significantly. rADF also reduced the cytotoxicity induced by anti-Fas IgM mAb which shows cytotoxicity quite similar to TNF. rADF (10 micrograms/ml) reduced 90% of the cytotoxicity by anti-Fas IgM mAb, without a detectable change either in Fas Ag expression (MFI 58.1 vs 53.3) or in the degradation of anti-Fas IgM mAb as determined by flow cytometric analysis. These findings indicated that the rADF-induced resistance to the cytotoxic effect of TNF and anti-Fas mAb was not related to the modulation of the TNF receptor or Fas Ag.
Survival of human macrophages infected with Mycobacterium avium intracellulare correlates with increased production of tumor necrosis factor-alpha and IL-6.
Authors: Newman G W , Gan H X , McCarthy P L , Remold H G 
Published: December 2022

Abstract
The long term survival of peripheral blood derived human macrophages (M phi) from normal, healthy donors after infection with Mycobacterium avium intracellulare (MAI) correlates with the increased induction of TNF-alpha and IL-6 mRNA and protein by the infected M phi. This conclusion is based on the following observations: M phi from approximately 30% of the blood donors in our study die 3 to 4 days after inoculation (MAI-growth nonsupportive (NS], whereas M phi from the other donors survive inoculation with MAI for 7-10 days (MAI-growth supportive (S)). S-type M phi when infected with MAI had markedly increased amounts of TNF-alpha and IL-6 mRNA and protein when compared to NS-type M phi. The effect of LPS on the induction of TNF-alpha mRNA and protein was also significantly enhanced in S-type M phi in comparison to NS cells. In contrast, IL-1 beta mRNA and protein production had similar increases in both donor types when infected with MAI or stimulated with LPS. The phenotype of the donors in the amount of TNF-alpha and IL-6 produced in response to MAI infection remained stable for a period of more than 1 yr. Pretreatment of NS M phi with recombinant human granulocyte-macrophage-CSF, but not IFN-gamma, however, converted NS M phi into a S-type cell phenotype. These granulocyte-macrophage-CSF pretreated NS M phi survived infection with MAI for a longer period of time and also had increased production of both TNF-alpha and IL-6 mRNA and protein. Cultures of S-type M phi infected with MAI had higher numbers of intracellular bacteria when compared to cultures of NS-infected M phi. Thus, increased survival of MAI-infected human M phi in vitro is correlated to increased production of TNF-alpha and IL-6 in response to infection with MAI.
Regulation of HILDA/LIF gene expression in activated human monocytic cells.
Authors: Anegon I , Grolleau D , Soulillou J P 
Published: December 2022

Abstract
We have previously shown that human monocytes express HILDA/LIF gene and its protein product upon stimulation. In the present study we have investigated some of the possible mechanisms involved in the regulation of HILDA/LIF gene expression in activated human monocytes and compared them to those of granulocyte colony-stimulating factor (G-CSF) and IL-1 beta gene expression. In the absence of added stimuli HILDA/LIF mRNA was barely detectable in isolated monocytes. HILDA/LIF mRNA accumulation was weakly induced by stimuli such as LPS or phorbol ester. However, a synergy was observed when each stimulus was used in combination with 1,25-dihydroxyvitamin D3. Nuclear run-on analysis did not detect an increase in HILDA/LIF gene transcription upon stimulation with LPS or phorbol ester in combination with 1,25-dihydroxyvitamin D3. HILDA/LIF mRNA half-life showed an increase when phorbol ester and 1,25-dihydroxyvitamin D3 were used in combination over that obtained for each stimuli alone. HILDA/LIF mRNA expression was largely inhibited when monocytes were stimulated in the presence of cycloheximide (CHX) added either at the onset or 4 h after the beginning of the stimulation period. When CHX was added at later time points, 2 h before cell harvesting, HILDA/LIF mRNA levels were superinduced when compared with those in cells stimulated in the absence of CHX. This superinduction can be at least partially explained by post-transcriptional mechanisms, since HILDA/LIF mRNA half-life in CHX-superinduced cells was significantly increased when compared with values on stimulated CHX-untreated cells. In contrast to HILDA/LIF, G-CSF and IL-1 beta mRNA accumulation showed a different response pattern to the same stimuli, and a augmentation of their gene transcription was detected by the run-on technique in activated monocytic cells when compared with controls. Furthermore, G-CSF and Il-1 beta mRNA levels were superinduced in monocytes stimulated in the presence of CHX from the onset of the stimulation period. These studies indicate that, when compared to G-CSF and IL-1 beta, the expression of HILDA/LIF gene is under the control of relatively specific regulatory mechanisms. HILDA/LIF gene expression is controlled by newly synthesized proteins acting at early and late time points of the stimulation period and with opposite effects on HILDA/LIF mRNA levels. Finally, HILDA/LIF mRNA levels are regulated by post-transcriptional mechanisms of mRNA stabilization probably controlled through labile newly synthesized proteins.
Gene expression of the A- and B-chain of mouse C1q in different tissues and the characterization of the recombinant A-chain.
Authors: Petry F , Reid K B , Loos M 
Published: December 2022

Abstract
Immunoscreening of a mouse macrophage cDNA library with an anti-mouse C1q-antibody resulted in the isolation of cDNA clones. The deduced amino acid sequence was homologous to the A-chain of human C1q. Homology on the DNA level was found to be 76% and on the protein level 72% thus it appeared the clones coded for the mouse C1q A-chain. An immunoblot of murine serum C1q separated by SDS-PAGE was detected with an A-chain specific antibody that had been affinity purified on recombinant mouse C1q A-chain expressed in Escherichia coli. The antibody preparation reacted exclusively with the mouse C-chain (as defined by SDS-PAGE). Northern blot analysis with strand-specific cDNA probes coding for the A- and B-chain of murine C1q showed that mouse peritoneal macrophages produced the highest concentration of C1q gene transcripts. RNA from mouse spleen, thymus, heart, and brain gave substantial hybridization signals, whereas RNA preparations from liver, kidney, lung, and small intestine appeared to contain only trace amounts of C1q mRNA. In a Northern blot analysis of different guinea pig cells and tissues, only RNA preparations from peritoneal macrophages hybridized with the mouse C1q probes. These results indicate that macrophages are a major site of C1q biosynthesis.
VDJ genes in VHa2 allotype-suppressed rabbits. Limited germline VH gene usage and accumulation of somatic mutations in D regions.
Authors: Short J A , Sethupathi P , Zhai S K , Knight K L 
Published: December 2022

Abstract
In this study we investigate the molecular genetic basis for VHa- Ig. Knowing that the expression of VHa allotype Ig is suppressed by neonatal injection of rabbits with anti-VHa allotype antibody, and that the decreased level of VHa allotype Ig, VHa+, in the suppressed rabbits is compensated for by an increase in VHa- Ig, we determined the nucleotide sequences of 41 VDJ genes from a2/a2 rabbits neonatally suppressed for the expression of a2 Ig. We compared these nucleotide sequences to each other and identified two groups of VH sequences. We predict that the molecules of each group are encoded by one germline VH gene. Inasmuch as VHa+ Ig is encoded predominantly by one germline VH gene, VH1, it appears that more than 95% of the VDJ repertoire of rabbits may be encoded by as few as three germline VH genes. A genomic VDJ gene whose VH sequence was similar to those of group I molecules was expressed in vitro and was shown by ELISA to encode molecules of the VHa- allotype, y33. Analysis of the D regions in the VDJ gene indicated that germline D2b and D3 gene segments were preferentially used in the VDJ gene rearrangement. A comparison of sequences of D regions of the 41 VDJ gene rearrangements in 3-, 6-, and 9-wk-old rabbits to sequences of germline D gene segments showed an accumulation of mutations in the D region. Inasmuch as we have previously shown that V regions of rabbit VDJ genes are diversified, in part, by somatic gene conversion, it appears now that rabbit VDJ genes diversify by a combination of somatic mutation and somatic gene conversion.
Clonal anergy blocks the response to IL-4, as well as the production of IL-2, in dual-producing T helper cell clones.
Authors: Mueller D L , Chiodetti L , Bacon P A , Schwartz R H 
Published: December 2022

Abstract
In this report we extend the in vitro clonal anergy model to examine the regulation of proliferation in T cells that secrete both IL-2 and IL-4. Newly cloned Ag-specific murine T cells are shown to depend on both IL-2 and IL-4 synthesis for maximal proliferation. Whereas IL-2 responsiveness is constitutive in these cells, IL-4 responsiveness develops only after Ag and APC stimulation. Remarkably, proliferation of these cells to Ag is sensitive to inhibition by clonal anergy, even though IL-4 synthesis remains inducible. Anergy in these cells is associated with an inability to respond to IL-4, in addition to the development of an IL-2 production defect. The results suggest that anergy induction may be capable of preventing the clonal expansion of autoreactive T cells producing both IL-2 and IL-4 in vivo.
The preference for switching to IgA expression by Peyer's patch germinal center B cells is likely due to the intrinsic influence of their microenvironment.
Authors: Weinstein P D , Cebra J J 
Published: December 2022

Abstract
This study was aimed at determining whether the chronically activated physiologic state of Peyer's patch (PP) tissue is primarily responsible for the IgA isotype preference expressed by PP germinal centers (GC) and memory B cells. We have used reovirus type 1/Lang to stimulate acute, de novo GC reactions in lymph nodes (LN) or PP to test the possibility that the surface (s)IgA component of enteric responses is peculiar to the local gut microenvironment whether or not PP are in a state of chronic activation. GC were raised in PP of germ-free mice by oral administration of virus and in lymph nodes (LN) of conventionally reared mice by local parenteral infection. Transient GC reactions were found to develop with similar time courses in both PP and LN after both primary and secondary local infections with reovirus. sIgA+ B cells, which were the major non-sIgM+/sIgD+ population found to arise in GC of PP, were not found in the LN. In LN, sIgG1+ B cells comprised the predominant non-IgM/IgD bearing population that arise after local infection. Lymphoid fragment cultures of PP initiated in vitro as early as 5 days after in vivo infection contained detectable secreted reovirus-specific IgA, whereas IgG1 but no IgA was found in LN cultures. Northern blot analysis to detect C alpha and C gamma 1 germline transcripts further substantiated a site-related bias in the expression of non-IgM/IgD isotypes that was manifest within a few days after infection. In summation, these observations taken together suggest that the preference for generating sIgA+ B cells in PP may be the result of intrinsic features of their gut microenvironment.
Expression and synthesis of cross-reactive idiotypic antibodies by peripheral blood lymphocytes and their suppression by anti-idiotypes in patients with IgA nephropathy.
Authors: González-Cabrero J , de Nicolas R , Hernando L , Egido J 
Published: December 2022

Abstract
We have recently described that patients with IgA nephropathy present high serum levels of anti-BSA idiotypic antibodies that were well correlated with the existence of hematuria. Furthermore, these Id were found in circulating and renal deposited immune complexes. In the present work, we examined the expression of surface idiotypic determinants on PBL by flow cytometry and their in vitro production, using as reagent anti-idiotypic antibodies previously well characterized. The presence of cross-reactive Id-bearing cells was observed in 5 out of 6 patients studied, with frequencies ranging from 3 to 12% of lymphocytes. After 7 days of culture, the spontaneous synthesis of idiotypic antibodies by PBL was found elevated in 6 out of 13 (46%) patients. A major Id cell expression and production was noted in patients with active disease as defined by hematuria. The preincubation of PBL with 20 and 50 micrograms of anti-idiotypic antibodies/2 x 10(6) cells for 3 days induced a significant inhibition of cross-reactive Id production in a dose-dependent fashion, with a degree of suppression between 12 and 50% in five out of six patients studied. In the above assays, as negative controls, we used the anti-Id antibodies previously adsorbed on an Id-Sepharose column. On the whole, these results suggest that patients with IgA nephropathy present dysfunctions in the Id-Anti-Id network that could play an important role in the pathogenesis of this disease.
Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease.
Authors: Marcelletti J F , Ohara J , Katz D H 
Published: December 2022

Abstract
The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
The VLA-4/VCAM-1 pathway is involved in lymphocyte adhesion to endothelium in rheumatoid synovium.
Authors: van Dinther-Janssen A C , Horst E , Koopman G , Newmann W , Scheper R J , Meijer C J , Pals S T 
Published: December 2022

Abstract
Lymphocyte migration to inflammatory sites is an essential factor in the pathogenesis of chronic inflammation. An ensemble of adhesion receptors mediating lymphocyte-endothelial cell recognition and binding are thought to play a crucial role in this process. In the present study, we have explored the molecular basis of lymphocyte adhesion to endothelium in the synovial membrane of patients with rheumatoid arthritis. We established that the very late antigen-4 [VLA-4 (CD49d)] and the vascular cell adhesion molecule-1 (VCAM-1) are important mediators of binding to synovial endothelium of resting and, to a greater extent, of activated T lymphocytes, whereas the leukocyte-function associated antigen-1 [LFA-1 (CD11a/18)]/intercellular adhesion molecule-1 [ICAM-1 (CD54)] pathway is less important in this interaction. In contrast to its prominent role in lymphocyte interaction with endothelium in rheumatoid synovium, the VLA-4/VCAM-1 pathway does not significantly contribute to lymphocyte adhesion to peripheral lymph node high endothelial venule. Thus, the VLA-4/VCAM-1 pathway may be of primary importance in mediating lymphocyte adhesion to inflamed endothelium and in lymphocyte homing to rheumatoid synovium.