bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vimentin expression is differentially regulated by IL-2 and IL-4 in murine T cells.
Authors: Hornbeck P V , Garrels J I , Capetanaki Y , Heimer S 
Published: December 2022

Abstract
IL-2 and IL-4 are T cell growth factors that are produced by different T cell subsets and have distinct roles in lymphocyte biology. Despite their importance in the immune system, little is known about the genes that these lymphokines may specifically control and the interaction of these lymphokines in regulating the expression of their target genes. In this paper, we use the factor-dependent murine T cell line (CT.4R) to investigate the interaction of IL-2 and IL-4 in regulating gene expression. We report that the intermediate filament protein vimentin is differentially regulated by these lymphokines. Cells grown in IL-2 typically express 10- to 20-fold more vimentin and vimentin RNA than those grown in IL-4, but express similar levels of other cytoskeletal proteins including actin and tubulin. Vimentin was specifically induced by IL-2 and apparently suppressed by IL-4 in normal lymph node T cells, suggesting that its differential regulation by these lymphokines is physiologically relevant. We investigated the synergy between IL-2 and IL-4 in regulating the expression of vimentin RNA and compared it to that of two other lymphokine-responsive genes, pancreatic lipase and the IL-2R alpha subunit. Complex regulatory interactions were revealed: IL-4 suppressed the ability of IL-2 to induce vimentin RNA but not IL-2R alpha RNA, whereas IL-2 inhibited the ability of IL-4 to induce lipase RNA. These results indicate that IL-2 and IL-4 can cross-regulate lymphokine-responsive genes and can simultaneously exert both positive and negative regulation of different genes within the same cell.
Characterization of murine T cell responses to peptides of the variable region of self T cell receptor beta-chains.
Authors: MacNeil D , Fraga E , Singh B 
Published: December 2022

Abstract
Immunization with peptides of the TCR may regulate cellular immune responses that are dominated by a particular TCR. However, no extensive study of the immunogenicity of peptides of different regions of the V beta chain of the TCR has been done. We have tested the immunogenicity of several V beta peptides in several strains of mice and characterized the cellular response to these peptides. We examined the ability of six strains of mice of H-2b, H-2d, or H-2k and of mouse lymphocyte stimulatory (Mls)-1a or Mls-1b haplotypes to respond to several peptides of the V beta 6 region and an NH2-terminal peptide of other V beta of the TCR. These include V beta 6 peptides 1-20, 32-48, 39-60, 48-75, 58-75, and V beta 3, V beta 8.1, and V beta 8.3 peptides 1-20. The various mouse strains respond to these peptides independently of deletion of V beta 6+ T cells from peripheral lymphocytes. All of the Mls deleting and nondeleting strains tested respond weakly to one peptide of V beta 6, V beta 6(39-60). Antibody titers were also demonstrated in BALB/c and DBA/2J to V beta 6(1-20), V beta 6(39-60) and V beta 6(48-75), but not to V beta 6(32-48). We demonstrated that T cells responding to V beta 6(32-48) produce IL-2 and IFN-gamma, consistent with the Th1 subset of T cells. None of the antipeptide antibodies recognized the intact V beta 6 TCR on the cell surface. In vitro antibody blocking studies with TCR peptides show that these peptides are presented by class II MHC to CD4+ T cells. We conclude that the T cell and B cell repertoires contain cells able to respond to peptides of self TCR and immunization with peptides induces CD4+ T cells and that these cells may have an immunoregulatory role.
Cytolytic activity of murine IL-2-producing CD4+ and CD8+ T cell clones cycles in response to IL-2.
Authors: McKisic M D , Lancki D W , Cronin D C , Fitch F W 
Published: December 2022

Abstract
Alloreactive or OVA-reactive cloned murine CD4+ or CD8+ T cells that produce IL-2 exhibit greatly reduced cytolytic activity after being cultured with high concentrations of rIL-2. Furthermore, such cells fail to produce lymphokines or proliferate when stimulated with Ag. The duration of this unresponsiveness to Ag correlates with the concentration of rIL-2 to which the cells were exposed; higher concentrations of rIL-2 prolong the period of unresponsiveness. The presence of ionomycin during the cytolytic assay restores lytic activity to cells rendered unresponsive by exposure to rIL-2. These results suggest that rIL-2-induced unresponsiveness to Ag is a consequence of impairment of a calcium-dependent signal important for cytolysis, proliferation, and lymphokine production. Thus, IL-2 appears to be an important lymphokine that regulates T cell responses downward as well as upward.
Characterization of the promoter region of the membrane cofactor protein (CD46) gene of the human complement system and comparison to a membrane cofactor protein-like genetic element.
Authors: Cui W , Hourcade D , Post T , Greenlund A C , Atkinson J P , Kumar V 
Published: December 2022

Abstract
Membrane cofactor protein (MCP; CD46) is a widely expressed C regulatory protein that inhibits C activation on self-tissue. MCP binds C3b and C4b deposited on autologous cells and then serves as a cofactor for their inactivation by limited proteolytic cleavage. To characterize the DNA sequence elements responsible for controlling MCP expression, the 5' flanking region of the human MCP gene was cloned. Sequencing of 1350 nucleotides upstream from the ATG codon revealed a GC-rich region in the initial 500 nucleotides that is especially rich in the CpG dinucleotide. A CAAT box in reverse orientation, surrounded by four putative SP1 binding sites but lacking a typical TATA element, was within the first 200 nucleotides of this GC-rich region. The major transcriptional initiation site for HeLa cells, determined by primer extension and S1 nuclease protection analyses, was located 105 nucleotides from the translational start site. This overall orientation of the promoter region is characteristic of "housekeeping" genes. The MCP promoter region was further examined in HEp-2 cells by the chloramphenicol acetyltransferase (CAT) reporter gene assay, using various constructs derived from the 5' region of the MCP gene. The MCP promoter activity was confined to the GC-rich region from -624 to +96 (start site of transcription being +1). Inclusion of an AT-rich sequence from -624 to -1204 resulted in a 42% reduction in CAT activity suggesting that an inhibitor is present among the AT-rich sequences. The 5' flanking region of a highly homologous partial duplication of the MCP gene was also cloned and sequenced, and various constructs were assessed in the CAT reporter system. Many of the functionally relevant sequences seen in MCP are also found in the MCP-like 5' UT region, which is 85% homologous to MCP. The most striking difference was a 224 nucleotide deletion that was upstream from the corresponding MCP region harboring most of the promoter activity. Although expression of an MCP-like protein has not been reported, the MCP-like promoter region produced promoter activity comparable with that of MCP. These results serve as a basis for subsequent analyses of the expression of MCP in various cells and tissues and for understanding the mechanism of its modulation in inflammatory conditions. Also, through a comparison of the 5' region of MCP with other genes in the regulators of C activation gene cluster (at 1 q32), we propose a model for the evolution of the promoters in this tight linkage group.(ABSTRACT TRUNCATED AT 400 WORDS)
Prevention of autoimmune type I diabetes by CD4+ suppressor T cells in superantigen-treated non-obese diabetic mice.
Authors: Kawamura T , Nagata M , Utsugi T , Yoon J W 
Published: December 2022

Abstract
The development of autoimmune type I diabetes in the NOD mouse appears to be controlled by both genetic and environmental factors. This investigation was initiated to determine whether exogenous superantigens, as environmental factors, can influence the development of diabetes. Several staphylococcal enterotoxins (SE) (SEA, SEC1, SEC2, or SEC3), which are known superantigens, were injected i.v. into female NOD mice at 4 and 10 wk of age. At 32 wk of age, the incidence of diabetes in the SE-treated mice ranged from 6 to 12.5%; this was significantly lower than that of mice treated with PBS--64%. There was no significant difference in effectiveness among the various SE used. SE induced a modest decrease in T lymphocytes bearing specific V beta TCR 2 wk after injection, but this effect did not persist past 4 wk. To elucidate the mechanism of the SE effect, suppressor activity in SE-treated mice was evaluated. Splenocytes from SE-treated mice inhibited the transfer of diabetes by splenocytes from acutely diabetic NOD mice when injected into irradiated young NOD mice; only 10% became diabetic. In contrast, 83% of the mice receiving splenocytes from PBS-treated control mice became diabetic. Suppressor activity of splenocytes from SE-treated mice was diminished by the depletion of CD4+ T cells, but not by the depletion of CD8+ T cells, indicating that the suppressor cells belonged to the CD4+ T class of lymphocytes. On the basis of these observations, we conclude that exogenous superantigens activate CD4+ suppressor T cells, leading to the prevention of autoimmune type I diabetes in NOD mice.
Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro.
Authors: Schulz B S , Michel G , Wagner S , Süss R , Beetz A , Peter R U , Kemény L , Ruzicka T 
Published: December 2022

Abstract
IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. Recently it has been shown to influence several functions of keratinocytes, including HLA-DR expression, chemotaxis, and proliferation by binding to a specific receptor. Because psoriasis vulgaris is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its receptor in normal and psoriatic epidermis using semiquantitative reverse-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also investigated as potential growth-promoting stimuli in psoriatic epidermis. IL-8 mRNA was only detected in lesional psoriatic epidermis, and IL-8R-specific mRNA was found to be 10 times increased in lesional psoriatic epidermis. There was no significant difference in the protooncogene mRNA levels. In order to test the relevance of the massively increased IL-8R levels in psoriatic epidermis, we investigated the effect of the antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expression. FK-506 dose dependently inhibited IL-8R expression and function. Our data suggest that in psoriatic skin, elevated IL-8 levels and markedly increased IL-8R expression may act in concert to induce the cardinal signs of psoriasis--epidermal hyperproliferation and leukocyte infiltration. IL-8R may prove a molecular target for antipsoriatic drugs such as FK-506.
Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains.
Authors: Parker K C , Bednarek M A , Coligan J E 
Published: December 2022

Abstract
A method to predict the relative binding strengths of all possible nonapeptides to the MHC class I molecule HLA-A2 has been developed based on experimental peptide binding data. These data indicate that, for most peptides, each side-chain of the peptide contributes a certain amount to the stability of the HLA-A2 complex that is independent of the sequence of the peptide. To quantify these contributions, the binding data from a set of 154 peptides were combined together to generate a table containing 180 coefficients (20 amino acids x 9 positions), each of which represents the contribution of one particular amino acid residue at a specified position within the peptide to binding to HLA-A2. Eighty peptides formed stable HLA-A2 complexes, as assessed by measuring the rate of dissociation of beta 2m. The remaining 74 peptides formed complexes that had a half-life of beta 2m dissociation of less than 5 min at 37 degrees C, or did not bind to HLA-A2, and were included because they could be used to constrain the values of some of the coefficients. The "theoretical" binding stability (calculated by multiplying together the corresponding coefficients) matched the experimental binding stability to within a factor of 5. The coefficients were then used to calculate the theoretical binding stability for all the previously identified self or antigenic nonamer peptides known to bind to HLA-A2. The binding stability for all other nonamer peptides that could be generated from the proteins from which these peptides were derived was also predicted. In every case, the previously described HLA-A2 binding peptides were ranked in the top 2% of all possible nonamers for each source protein. Therefore, most biologically relevant nonamer peptides should be identifiable using the table of coefficients. We conclude that the side-chains of most nonamer peptides to the first approximation bind independently of one another to the HLA-A2 molecule.
Tyrosine kinase-dependent assembly of actin plaques linking Fc epsilon R1 cross-linking to increased cell substrate adhesion in RBL-2H3 tumor mast cells.
Authors: Pfeiffer J R , Oliver J M 
Published: December 2022

Abstract
RBL-2H3 rat tumor mast cells form monolayers on various surfaces without assembling specialized adhesion structures at the cell substrate interface. Incubation of RBL-2H3 cells with Ag that cross-link the high affinity IgE receptor, Fc epsilon R1, activates at least two receptor-associated protein tyrosine kinases, Syk and Lyn, and elicits secretion and F-actin assembly, membrane ruffling, and increased spreading and adhesion. Herein, we report that Fc epsilon R1 cross-linking also causes the assembly in cell monolayers of a network of F-actin-rich plaques that form footlike processes at contact sites between the plasma membrane and the underlying substratum. Sheets of F-actin-rich ventral plasma membrane-bearing actin plaques are left on the substrate when monolayers of activated cells are displaced by incubation with ZnCl2 followed by shearing in a stream of buffer; in contrast, most unstimulated cells are completely displaced or leave only fragile membrane fragments. These observations link actin plaque assembly to increased cell substrate adhesion. Actin plaques disassemble rapidly in the presence of monovalent hapten, indicating their dependence on continued Fc epsilon R1 cross-linking. They accumulate antibody to phosphotyrosine and disassemble rapidly in the presence of the protein tyrosine kinase inhibitor, piceatannol, indicating their additional dependence on tyrosine kinase activation. Structures resembling actin plaques form when RBL-2H3 cell monolayers are incubated with the protein tyrosine phosphatase inhibitor, vanadyl hydroperoxide, in the presence of PMA, which increases actin polymerization. It is likely that the tyrosine kinase-dependent assembly of actin plaques plays an important role in linking the activation of signaling receptors to adhesive responses in RBL-2H3 and other immune system cells.
Specificity and class distribution of Fc gamma R-specific autoantibodies in patients with autoimmune disease.
Authors: Boros P , Odin J A , Chen J , Unkeless J C 
Published: December 2022

Abstract
To investigate the prevalence of autoantibodies directed against Fc gamma RII (CD32) and Fc gamma RIII (CD16), 151 serum samples from patients with different autoimmune diseases and 25 samples obtained from healthy individuals were assayed by ELISA on microtiter plates coated with recombinant truncated Fc gamma RII and Fc gamma RIII protein. Class specificity was defined with anti-IgG, anti-IgM, and anti-IgA reagents. High titers of circulating IgM autoantibodies reacting with both Fc gamma RII and Fc gamma RIII were characteristic for SLE and rheumatoid arthritis patients. Sera from patients with Raynaud's syndrome showed predominantly IgG reactivity with Fc gamma RIII. Sera from patients with progressive systemic sclerosis showed both IgG and IgM Fc gamma RII and Fc gamma RIII reactivity. Many patients diagnosed with degenerative osteoarthritis also had IgG autoantibodies, directed primarily against Fc gamma RII with lesser reactivity toward Fc gamma RIII. Further study is needed to correlate these findings to clinical characteristics of the different diseases.
Effects of syngeneic anti-IgE antibodies on the development of IgE memory and on the secondary IgE response.
Authors: Haba S , Nisonoff A 
Published: December 2022

Abstract
The prolonged inhibition of IgE synthesis in mice caused by perinatal inoculation of IgE is attributable, at least in part, to the formation of anti-IgE antibodies. The induction of unresponsiveness with respect to IgE synthesis requires that IgE be administered during a brief interval (2 to approximately 10) days after birth, that corresponds with the time period during which anti-IgE antibodies are induced. Passive administration of syngeneic anti-IgE also inhibits IgE synthesis. We have now investigated the effect of anti-IgE on the induction of memory for IgE production and on secondary IgE responses. Syngeneic anti-IgE antibodies were found to inhibit secondary IgE responses directly during immunization or after adoptive transfer of primed cells. Anti-IgE did not, however, prevent the induction of memory cells for IgE synthesis or cause the loss of memory for IgE synthesis. Inhibition of a secondary IgE response was found to require the presence of anti-IgE and was lost when anti-IgE antibodies were cleared from the mouse. After the transfer of primed cells and secondary challenge anti-IgE was inhibitory only when given during the first 3 to 5 days, after which the primed cells became resistant to inhibition. The failure of anti-IgE to prevent the induction of IgE memory cells is discussed in terms of class switches that occur during the transition from IgM to IgE production.
Immunobiologic and biochemical properties of mutants of toxic shock syndrome toxin-1.
Authors: Murray D L , Prasad G S , Earhart C A , Leonard B A , Kreiswirth B N , Novick R P , Ohlendorf D H , Schlievert P M 
Published: December 2022

Abstract
Toxic shock syndrome (TSS) is a multisystem illness caused mainly by Staphylococcus aureus producing TSS toxin-1 (TSST-1). A variant of TSST-1 has been isolated from ovine mastitis S. aureus. This toxin, TSST-ovine (TSST-O) is only weakly T cell mitogenic, is nonpyrogenic, does not enhance endotoxin shock, and does not cause TSS in the miniosmotic pump model. The sequence of the ovine gene (tstO) differs from the TSST-1 gene (tstH) by 14 nucleotides that change seven amino acids in the mature protein of which two are in the C-terminal half. A gene fusion containing half of both tstH and tstO was made and cloned into S. aureus. The fusion protein contained the two C-terminal amino acid differences that are in TSST-O at residues 132 and 140. The fusion protein was not T cell mitogenic and did not elicit TSS in two rabbit models. Additional experiments used mutagenesis to change the lysine residue at position 132 of TSST-O to glutamate (TSST-OK132E), as exists in TSST-1, and to change the lysine residue of the human-ovine fusion at position 132 to glutamate (TSST-11140T). Both mutants were pyrogenic, enhanced endotoxin shock, and caused TSS in the miniosmotic pump model. However, the proteins were only partially T cell mitogenic. The restoration of lethality of TSST-O and the human-ovine fusion by changing the lysine to glutamate, as exists in TSST-1, indicates that residue 132 is important in lethality. The failure to regenerate complete T cell mitogenicity of the same mutants indicates that residues 132 and 140 are important for that activity.
Serine phosphorylation of a 67-kDa protein in human T lymphocytes represents an accessory receptor-mediated signaling event.
Authors: Henning S W , Meuer S C , Samstag Y 
Published: December 2022

Abstract
Phosphorylation on serine residues of a 67-kDa cytoplasmic protein (p67) occurs as an early signaling event after stimulation of resting human T cells via CD2 but not via TCR/CD3. Phosphorylation of p67 is, however, not restricted to CD2 stimulation because it can also be induced by costimulation through CD4 and CD8 coreceptors when approximated to the TCR-CD3 complex, suggesting a common signaling mechanism for these accessory receptors of the Ig superfamily. Because late functional responses of T cell activation like IL-2 production and DNA synthesis correlate with phosphorylation of p67, this intracellular event may represent an accessory receptor-mediated costimulatory second signal for human T cell activation. The biochemical characteristics (m.w. and isoelectric point) of p67 are identical with those of the actin binding protein L-plastin (Fimbrin), a cytoplasmic protein that contains two Ca2+ binding sites and a calmodulin binding domain. Moreover, p67 reacts specifically with an L-Plastin (Fimbrin) antiserum.
Two processing pathways for the MHC class II-restricted presentation of exogenous influenza virus antigen.
Authors: Pinet V , Malnati M S , Long E O 
Published: December 2022

Abstract
The natural Ag influenza virus A was used to test the requirements for the HLA-DR1-restricted presentation of the epitopes 18-29 in the matrix protein and 307-318 in the hemagglutinin protein. CD4+ cytotoxic T cell clones of similar efficiency were used to detect presentation of these two epitopes. Presentation of the matrix epitope by APC pulsed with either inactivated virus particles or purified soluble protein followed the classical pathway in that 1) it required invariant chain expression, 2) it was blocked by inhibition of protein synthesis, and 3) it was dependent on a function(s) encoded in the MHC class II region. These characteristics suggest that peptides corresponding to the matrix epitope can only load onto newly synthesized class II molecules that were targeted to a processing compartment by the invariant chain. In contrast, presentation of the hemagglutinin epitope processed from virus particles followed a different pathway. First, presentation of hemagglutinin was independent of invariant chain expression. Second, a human B lymphoblastoid cell line in which protein synthesis was inhibited for 9 h was still able to present hemagglutinin even at very low doses of Ag. Third, a DR1-transfected mutant B cell line missing the MHC class II region was able to present hemagglutinin. Thus, mature class II alpha beta molecules can acquire immunogenic peptides derived from intact natural Ags for presentation to CD4+ T cells. This pathway may be useful for the binding of peptides derived from Ags that are rapidly degraded upon uptake into APC.