bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of granulomatous experimental autoimmune thyroiditis in mice with in vitro activated effector T cells and anti-IFN-gamma antibody.
Authors: Stull S J , Sharp G C , Kyriakos M , Bickel J T , Braley-Mullen H 
Published: January 2023

Abstract
Experimental autoimmune thyroiditis (EAT) can be induced in mice after the transfer of mouse thyroglobulin (MTg)-sensitized donor spleen cells that have been activated in vitro with MTg. CD4+ T cells are required for the transfer of EAT in this model. Because CD4+ T cells produce various lymphokines, such as IFN-gamma, that may be involved in the activation or regulation of the immune response to MTg and the development of EAT, the present study was undertaken to determine whether a neutralizing mAb to IFN-gamma could modulate the induction or expression of EAT. The anti-IFN-gamma mAb XMG-1.2 had no effect on sensitization of donor cells. However, addition of XMG-1.2 mAb during in vitro activation of MTg-primed spleen cells resulted in more severe EAT in recipient mice. The thyroid lesions in recipients of cells cultured with MTg and XMG-1.2 mAb also exhibited granulomatous changes, which differed qualitatively from the predominantly lymphocytic cell infiltrates in recipients of cells cultured with MTg alone. Recipients of MTg-activated spleen cells also developed severe granulomatous EAT when they were given injections of XMG-1.2 mAb. The effects of XMG-1.2 could be neutralized by IFN-gamma. Recipients of cells cultured in the presence of XMG-1.2 mAb had augmented autoantibody responses, although there were no apparent differences in the IgG subclass distribution of the anti-MTg autoantibody responses. These studies suggest that neutralization of endogenous IFN-gamma results in increased activity of cells capable of inducing granulomatous EAT in mice.
A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene.
Authors: Van Es J H , Aanstoot H , Gmelig-Meyling F H , Derksen R H , Logtenberg T 
Published: January 2023

Abstract
We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.
Ricinoleated Streptococcic Vaccines
Authors: Larson W. P. 
Published: January 2023

Abstract
This brief paper is in reply to a recent article by Kozlowski (1), in which he reports the results of studies on the immunizing properties of ricinoleated streptococcic (scarlet fever) cultures.
Kozlowski observed ulcerations in his experimental animals at the site of the injection, and concluded that the reaction was due to the sodium ricinoleate, which he used as a detoxifying agent.
Kozlowski states that he purified the ricinoleic acid, from which the soap was prepared, through the barium salts. This undoubtedly is the key to his difficulty. I have found that soap prepared from fatty acids which have been purified with barium, invariably causes abscesses, since it is very difficult, and from a practical standpoint almost impossible, to remove the last trace of barium in the final purification processes. For this reason I have long since discontinued that method of purification.
Studies in Hypersensitiveness
Authors: Brown Aaron 
Published: January 2023

Abstract
The nature of the protective effect of the injection of pollen extracts in hay fever subjects is still unknown.
This mode of treatment of hay fever was introduced in medical practice after hay fever was recognized as a condition of hypersensitiveness, and it was looked upon as a procedure analagous in its operation to that of desensitization in anaphylaxis. However, recent studies from this department have shown that the prophylactic effect of the treatment is not due to a neutralization of the substances which appear to be responsible for the state of hypersensitiveness, because, at the end of a successful course of treatment, these substances (the atopic reagins) are not diminished in the blood and, in fact, they are sometimes increased.
These unexpected findings removed from consideration the only explanation of the phenomenon of protection that was compatible with our knowledge of the hypersensitive state and with the assumption that the protective effect of the injections is a specific one.
HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs.
Authors: DiBrino M , Tsuchida T , Turner R V , Parker K C , Coligan J E , Biddison W E 
Published: January 2023

Abstract
The potential value of peptide binding motifs of HLA class I molecules for the prediction of viral epitopes presented to T cells has been analyzed for two common HLA alleles. CTL generated against type A influenza virus recognize peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1 presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct peptide binding motifs with characteristic anchor residues were previously identified for each of these class I molecules based on the sequences of endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr; for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing the HLA-A1 binding motif were identified within the sequences of the NP and basic polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide binding assay. Two of the HLA-A1-binding peptides could sensitize target cells for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44-52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265-273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted influenza-immune CTL. Each peptide was also shown to be able to induce peptide-specific class I-restricted CTL in vitro, and the CTL generated against two of these peptides could specifically recognize virus-infected targets. Thus, these peptide binding motifs can be used to construct immunogenic synthetic epitopes which are capable of inducing antiviral T cell-mediated immune responses.
Identification of a novel population of CD8 alpha+ beta- bone marrow-derived dendritic epidermal cells. This unique population is subsequently outnumbered by thymus-independent expansion of the CD8 alpha+ beta+ dendritic epidermal cells.
Authors: Hayakawa J , Shiohara T , Moriya N , Arahari K , Nagashima M , Yagita H , Ishikawa H 
Published: January 2023

Abstract
Maturation of some T cell populations has been suggested to occur in epithelial tissues. The CD8 molecule, which is expressed as heterodimers made of alpha/beta-chains on virtually all peripheral T cells, is preferentially expressed as homodimers made only of alpha-chains on a subset of CD8+ mouse gut intraepithelial lymphocytes, which arise from bone marrow (BM) precursors in a thymus-independent mechanism. This unique population of CD8 alpha+ beta- T cells, however, has not been identified in other lymphoid tissues in normal adult mice. Because our previous study demonstrated that reconstitution of thymectomized irradiated mice with T cell-depleted BM cells resulted in the appearance of CD8+, TCR-alpha beta+ dendritic epidermal cells (DEC) and suggested that a proportion of the BM-derived DEC may mature within the epidermis, we asked whether the unique phenotype of CD8 alpha+ beta- could be detected among the CD8+ BM-derived DEC. In this report for the first time we identified this unique population of CD8 alpha+ beta- cells among the DEC. Although this population comprised the predominant fraction of the BM-derived DEC in the early post-transfer period (2 to 3 mo), gradual shift from the CD8 alpha+ beta+ phenotypes occurred during the late post-transfer period (4 to 6 mo) independently of the presence of the thymus. Kinetic studies on the BM-derived DEC revealed that this phenotypic shift could be caused by the subsequent expansion of the CD8 alpha+ beta+ DEC. In contrast, the CD8 alpha+ beta- population was the major subset of the BM-derived intraepithelial lymphocytes throughout the entire observation period and the phenotypic shift with age was never observed. These results indicate that CD8 alpha+ beta- cells are preferentially detected on T cells that home to the epithelial tissues and that in the epidermis, but not in the gut epithelia, the subsequent expansion of the CD8 alpha+ beta+ DEC would dilute the high number of the CD8 alpha+ beta- cells.
Avidity for antigen can influence the helper dependence of CD8+ T lymphocytes.
Authors: Heath W R , Kjer-Nielsen L , Hoffmann M W 
Published: January 2023

Abstract
To examine the influence of avidity on the helper dependence of CD8+ T cells, purified CD8+ T cells from transgenic mice expressing a TCR specific for H-2Kb were tested for their responsiveness to spleen cells expressing different densities of H-2Kb. High avidity interactions resulted in the induction of strong proliferative responses by purified CD8+ T cells. These cells synthesized their own IL-2 and IL-2R. By contrast, low avidity interactions failed to induce proliferation or detectable IL-2 synthesis, although IL-2R were induced and addition of rIL-2 induced a proliferative response. These results are consistent with a model in which TCR avidity for Ag can determine the helper dependence of a CD8+ T cell.
Keratinocyte-derived IL-7 serves as a growth factor for dendritic epidermal T cells in mice.
Authors: Matsue H , Bergstresser P R , Takashima A 
Published: January 2023

Abstract
Dendritic epidermal T cells (DETC) are CD3+, CD45+, CD4-, CD8-, TCR-V gamma 3/V delta 1+ T lymphocytes that reside in symbiosis with keratinocytes in mouse epidermis. To address mechanisms by which these cells survive and proliferate within the epidermal environment, we have tested the hypothesis that cytokines secreted by neighboring keratinocytes play relevant roles. The present study was conducted to determine whether keratinocytes produce biologically relevant amounts of IL-7, and, if so, to study its effects on DETC. The long term cultured DETC line, 7-17, and freshly isolated DETC exhibited dose- and time-dependent proliferative responses to rIL-7. These responses were blocked completely by anti-IL-7 antibodies, whereas anti-IL-2 had no effect, indicating that DETC respond to IL-7 by an IL-2-independent mechanism. Proliferative responses depended on the state of cell activation; DETC stimulated 2 to 5 days earlier with Con A proliferated optimally to added IL-7, whereas cells stimulated 10 days earlier did not proliferate. DETC that failed to proliferate responded to IL-7 by showing prolonged survival; cells maintained for 7 days with IL-7 alone retained their capacity to proliferate in response to Con A. Mouse epidermal cells and Pam 212 keratinocyte line both expressed IL-7 mRNA constitutively, as demonstrated by reverse transcription-polymerase chain reaction analyses. The production of IL-7 by mouse keratinocytes was also confirmed; Pam 212 culture supernatants supported DETC proliferation, and this activity was diminished by 50% with added anti-IL-7 antibodies. These results indicate that keratinocytes produce IL-7 in biologically relevant amounts, which, in turn, serve to promote the survival and growth of DETC. IL-7-mediated communication between epithelial cells and gamma delta T cells may represent one mechanism to sustain the indefinite residence of gamma delta T cells in epithelial tissues of mice.
Dissociation of the peptide-MHC class I complex limits the binding rate of exogenous peptide.
Authors: Ojcius D M , Abastado J P , Casrouge A , Mottez E , Cabanie L , Kourilsky P 
Published: January 2023

Abstract
Soluble, single-chain molecules for two MHC class I alleles, H-2Kd and H-2Kb, were used to analyze the kinetics of antigenic peptide binding to MHC. After MHC preloading with radiolabeled or fluorescent peptides, the observed rate of MHC-peptide complex dissociation increased after addition of an excess of unlabeled competitor peptide. Although exogenous peptides conforming to the allele-specific motif were required for the enhanced complex dissociation to occur, the dissociation rate of the complex was independent of exogenous peptide concentration. Similarly, the association rate of exogenous peptides was independent of concentration, reflecting the presence of low affinity peptides in the binding sites of the recombinant MHC proteins; the sequences of these endogenous peptides conform to the consensus motif for the MHC allele studied. Finally, the association rate of exogenous peptide decreased when MHC molecules were preloaded with high affinity peptides, and the binding of labeled high affinity peptide to isolated recombinant MHC was faster than the subsequent dissociation observed in the presence of competitor peptide. Taken together, these results imply that the rate of exogenous peptide binding is limited by the dissociation rate of the previously bound peptides.
Two separate mechanisms of T cell clonal anergy to Mls-1.
Authors: Yui K , Ishida Y , Katsumata M , Komori S , Chused T M , Abe R 
Published: January 2023

Abstract
T cell tolerance to superantigen can be mediated by clonal anergy in which Ag-specific mature T cells are physically present but are not able to mount an immune response. We induced T cell unresponsiveness to minor lymphocyte stimulations locus antigen (Mls)-1a in mice transgenic for TCR V beta 8.1 in three different systems: 1) injection of Mls-1a spleen cells, 2) mating with Mls-1a mice, and 3) bone marrow (BM) chimeras in which Mls-1a is present only on nonhematopoietic cells. CD4+8-V beta 8.1+ cells from all these groups did not proliferate in response to irradiated spleen cells from Mls-1a mice. We compared the response of these cells by T cell/stimulator cell conjugate formation, Ca2+ mobilization, and proliferation assays. The mechanisms underlying the unresponsiveness of these T cells appear to differ. CD4+8-V beta 8.1+ cells from Mls-1a spleen cell-injected mice mobilized cytoplasmic Ca2+ but proliferated at a reduced level in response to cross-linking with anti-TCR mAb. However, these cells formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a when activated B cells were used as stimulators, although they produced reduced levels of IL-2. In Mls-1a/b V beta 8.1 transgenic mice, a subset in CD4+8-V beta 8.1+ cells did not mobilize cytoplasmic Ca2+ after TCR cross-linking. Their conjugate formation, Ca2+ mobilization, or proliferation in response to Mls-1a on activated B cells was undetectable. Finally, CD4+8-V beta 8.1+ cells from the BM chimeras proliferated to TCR cross-linking at a partially reduced level and formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a on activated B cells. These features suggest that the mechanisms underlying the maintenance of anergy in Mls-1a spleen cell-injected mice are distinct from those in Mls-1a mice.
Third component of trout complement. cDNA cloning and conservation of functional sites.
Authors: Lambris J D , Lao Z , Pang J , Alsenz J 
Published: January 2023

Abstract
Of the 30 distinct complement proteins recognized to date, C3 is probably the most versatile and multifunctional molecule known, interacting with at least 20 different proteins. It plays a critical role in both pathways of complement activation and participates in phagocytic and immunoregulatory processes. Structural and functional analysis of C3 from different species, in addition to phylogenetic information, provides insights into the structural elements mediating the various functions. This study describes the cDNA cloning of one of two isoforms of the third complement component, C3-1, of rainbow trout (Salmo gairdneri) and the analysis of its functional sites. By screening a trout liver lambda gt11 library with anti-trout C3 chain-specific antibodies and polymerase chain reaction we have determined the cDNA sequence of trout C3-1. The obtained sequence is in complete agreement with the protein sequence of several tryptic peptides, corresponding to different regions of trout C3-1. C3-1 consists of 1640 amino acids with a calculated molecular mass of 181,497 Da. The sequence contains two potential N-glycosylation sites, one on each chain of C3. The deduced protein sequence showed 44.1, 43.3, 44.2, 44.9, 43.1, 43.8, 45.9, 29.9, and 33.1% amino acid identities to human, mouse rat, guinea pig, rabbit, cobra, frog, hagfish, and lamprey C3, whereas the identities to human C4, C5, and alpha 2M are 30.4, 28, and 22.9%, respectively. The trout C3 amino acid sequence shows clusters of high and low similarity to C3 from other species. In the regions of high similarity belong the C3 domains that contain the thiolester site and the properdin binding sites, whereas the regions that correspond to regions of human C3 where CR1 and CR2 bind show low amino acid sequence similarity. The deduced amino acid sequence shows that the C3 convertase cleavage site (Arg-Ser) is conserved in trout C3, whereas the factor I cleavage sites are Arg-Ala and Arg-Thr instead of Arg-Ser, which is found in the C3 of other species. Protein sequencing of the trout C3 fragments fixed on zymosan during complement activation confirmed the cleavage of trout C3 by trout C3 convertase and factor I at Arg-Ser and Arg-Thr, respectively.
cAMP activates the IL-5 promoter synergistically with phorbol ester through the signaling pathway involving protein kinase A in mouse thymoma line EL-4.
Authors: Lee H J , Koyano-Nakagawa N , Naito Y , Nishida J , Arai N , Arai K , Yokota T 
Published: January 2023

Abstract
Expression of the IL-5 gene in T cells is induced in response to Ag stimulation; however, functional analysis of the IL-5 gene has been limited by lack of an appropriate transfection assay to facilitate measurement of the IL-5 promoter activity in response to T cell activation signals. Here, we describe a transient transfection system with which the IL-5 promoter activity can be assayed quantitatively. Using mouse thymoma line EL-4 cells, which produce several lymphokines including IL-2, IL-3, IL-4, IL-10, and GM-CSF in response to PMA, the effect of cAMP on IL-5 production was examined. These cells produce a low level of IL-5 when stimulated with PMA alone; however, N6, O2-dibutyryl cAMP (Bt2cAMP), in combination with PMA, augmented by more than tenfold the IL-5 production at the mRNA and the protein levels. Likewise, a transient transfection assay revealed that Bt2cAMP activated the IL-5 promoter more than tenfold, in a PMA-dependent manner, thereby indicating that two signals, PMA and cAMP, are required for optimal activation of the IL-5 promoter. Activation of the IL-5 promoter in response to Bt2cAMP and PMA depends on the region spanning from nucleotide position -1,200 to +33 relative to the transcription initiation site. Action of cAMP on the IL-5 promoter is mimicked by cotransfection of the expression plasmid containing cDNA encoding the catalytic subunit of protein kinase A, hence, cAMP probably exerts its action through the signaling pathway that involves protein kinase A. In contrast, Bt2cAMP almost completely inhibited the PMA-dependent activation of the endogenous IL-2 gene as well as the transfected IL-2 promoter. These results indicate that the IL-5 gene in EL-4 cells is positively regulated by cAMP in a manner opposite that for the IL-2 gene.
Met-ase: cloning and distinct chromosomal location of a serine protease preferentially expressed in human natural killer cells.
Authors: Smyth M J , Sayers T J , Wiltrout T , Powers J C , Trapani J A 
Published: January 2023

Abstract
A cDNA clone encoding a human NK serine protease was obtained by screening a lambda-gt10 library from the Lopez NK leukemia with the rat natural killer Met-ase (RNK-Met-1) cDNA clone. In Northern blot analysis human Met-ase (Hu-Met-1) cDNA hybridized with a 0.9-kb mRNA in two human NK leukemia cell lines, unstimulated human PBMC, and untreated purified CD3-CD56+ large granular lymphocytes. Unlike other members of the granzyme family that are highly expressed in activated peripheral T cells, the Hu-Met-1 transcript was barely detected in a population of PMA and ionomycin or IL-2-treated high density T cells. Several in vitro cultured Burkitt lymphomas, chronic- and promyeloid leukemias, acute lymphoblastic leukemias, and colon and ovarian carcinomas and colon and ovarian carcinomas did not express Hu-Met-1 mRNA. Hu-Met-1 mRNA expression in a small number of human T cell tumor lines did not correlate with any particular phenotype or stage of development. The presence of Hu-Met-1 mRNA closely correlated with the Met-ase activity of cellular lysates prepared from these various human peripheral blood subsets and in vitro cultured cell lines. Met-ase activity detected in whole cell lysates of cytotoxic lymphocytes was associated with the cytoplasmic granules of these cells. The nucleotide sequence of the Hu-Met-1 cDNA clone encodes a predicted serine protease of 257 amino acids. The predicted protein is an active enzyme of 232 amino acids with a calculated unglycosylated m.w. of 27,100. Hu-Met-1 is 66% identical to RNK-Met-1 at the amino acid level. The human and rat mature protein sequences conserve the active site His, Asp, and Ser amino acids that form the catalytic triad of serine proteases, all 8 cysteine residues, and several amino acids critical in the formation of the substrate binding pocket. The gene for the Hu-Met-1 serine protease is located on chromosome 19, which distinguishes it from any other member of the human granzyme family.