bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor-beta modulates T cell-mediated encephalitis caused by Borna disease virus. Pathogenic importance of CD8+ cells and suppression of antibody formation.
Authors: Stitz L , Planz O , Bilzer T , Frei K , Fontana A 
Published: December 2022

Abstract
Borna disease is a virus-induced, immune-mediated encephalomyelitis based on a delayed-type hypersensitivity reaction. The severity of clinical symptoms after intracerebral infection of rats with Borna disease virus was reduced after treatment with transforming growth factor (TGF-beta 2). Intraperitoneal injection of the recombinant molecule, rTGF-beta 2, started on the day of infection at a dose of either 1 micrograms given every day or every other day for 8 consecutive days or 2 micrograms every third day, was found to result in the absence of typical Borna disease symptoms at 14 days after infection in most of the TGF-beta-treated rats, a time point at which all infected control animals not treated with rTGF-beta 2 showed distinct signs of Borna disease. The inhibition of the disease was paralleled by a significant reduction of the inflammatory reaction in the brain. However, the efficacy of treatment with rTGF-beta 2 was transient, because after day 21 only a slight or no reduction of the inflammatory reaction and, consequently, symptoms of Borna disease could be observed. Immunohistologic investigations revealed reduced CD4+ T cell numbers and no changes in macrophage counts in encephalitic lesions of rTG-beta treated rats. However, CD8+ cells were markedly decreased in the encephalitic lesions. Furthermore, the expression of MHC class II Ag was significantly reduced in the brain of rTGF-beta 2 treated Borna disease virus-infected rats, whereas MHC class I Ag expression was not. Most treated animals showed a reduction of Borna disease virus-specific serum antibodies, the result of an inhibition of the IgG response. The results presented here suggest a distinct influence of rTGF-beta 2 on T cell-mediated immune functions during the early phase of Borna disease virus-induced encephalomyelitis.
Specific pathogen-free BALB/cAn mice are refractory to plasmacytoma induction by pristane.
Authors: Byrd L G , McDonald A H , Gold L G , Potter M 
Published: December 2022

Abstract
Forty to sixty percent of conventionally (CON) raised BALB/cAnPt (BALB/c) mice develop plasmacytomas (PCT) when injected with three 0.5 ml i.p. injections of pristane. When CON-BALB/c mice were converted to specific pathogen free (SPF) status by foster nursing caesarean delivered term mice on C3H/HeN SPF mothers and maintained under strict SPF conditions, less than 5% of the mice developed pristane-induced PCT. FACS analysis of the cellular composition of oil granulomatous tissue revealed a dramatic influx of CD4+ cells in CON mice that was significantly reduced in SPF mice. Moreover, while both CON and SPF mice had similar patterns of gut flora colonization, only CON-BALB/c mice had occasional circulating antibodies to mouse hepatitis virus and Sendai viruses. Maintenance in strict SPF conditions, therefore, results in a prolonged state of relative Ag deprivation and a failure to continuously activate new T and B cell populations. The results suggest that PCT formation depends on exogenous antigenic stimulation and that the presence of minimal gut flora is insufficient to render these mice susceptible to PCT induction.
Identification and characterization of a T cell-inducing epitope of bovine ribonuclease that can be restricted by multiple class II molecules.
Authors: Chen J S , Lorenz R G , Goldberg J , Allen P M 
Published: December 2022

Abstract
An immunodominant epitope of bovine RNase restricted by I-Ek molecules was identified using a T cell hybridoma recognizing RNase. This epitope was localized to the peptide RNase(90-105). Single conservative amino acid substitutions were made at each of the positions 94 through 105. It was found that only at one position, Asn-103, were conservative substitutions not allowed. This residue was shown to be the critical residue in determining T cell specificity. The ability of RNase(90-105) and the well-defined T cell epitope, HEL(46-61) to stimulate mouse strains expressing different independent H-2 haplotypes was examined using a T cell proliferation assay. The response to HEL(46-61) was completely restricted to mice expressing an I-Ak molecule. In striking contrast, 6 of 10 different mouse strains, H-2b,f,k,q,s,u, mounted vigorous T cell responses to RNase(90-105). The response was restricted to both I-A and I-E molecules, including I-Ab, I-Af, I-Ek, I-Aq, and I-As. H-2d mice were nonresponders to RNase(90-105), which was shown to be due to the failure of RNase(90-105) to bind to I-Ad molecules. A variant RNase(90-105) peptide was generated, containing an I-Ad binding motif, that could bind to I-Ad molecules. Despite its ability to bind, this variant peptide was not able to stimulate a response in H-2d mice. This result demonstrates that the ability of a peptide to bind to an Ia molecule is necessary but not always sufficient for a response to occur. Thus, in contrast to the highly restricted HEL(46-61) determinant, the RNase(90-105) determinant is permissive in its binding to Ia molecules. These results show that in the universe of T cell inducing epitopes contains both highly restricted and broadly restricted epitopes are found.
IgE and IgG binding of peptides expressed from fragments of cDNA encoding the major house dust mite allergen Der p I.
Authors: Greene W K , Cyster J G , Chua K Y , O'Brien R M , Thomas W R 
Published: December 2022

Abstract
Large peptides expressed from cDNA fragments of a clone encoding the mite allergen Der p I were able to bind IgE and IgG in sera from allergic individuals. The binding was found for peptides from sequences throughout the molecule, with at least five regions, comprising residues 1-56, 53-99, 98-140, 166-194, and 188-222. The only limitation was that more than 30 amino acid residues were required for consistent binding. Each of seven sera examined showed a different profile of antibody binding to the peptides. For the most part the pattern of IgE and IgG binding to the peptides for each serum was similar, demonstrating a concordant repertoire. In 5/7 sera, however, IgG bound to some peptides which had little or no IgE binding activity, thus showing more diverse specificities. It is suggested that some divergence of repertoire can develop during the maturation of the B cell response.
Tumor necrosis factor-alpha regulates expression of receptors for formyl-methionyl-leucyl-phenylalanine, leukotriene B4, and platelet-activating factor. Dissociation from priming in human polymorphonuclear neutrophils.
Authors: O'Flaherty J T , Rossi A G , Redman J F , Jacobson D P 
Published: December 2022

Abstract
TNF-alpha enhances polymorphonuclear responses to many stimuli, including chemotactic peptide FMLP. It also promotes expression of FMLP receptors and thus may prime polymorphonuclear neutrophils to this and other agonists by up-regulating signal recognition molecules. However, we find that the cytokine's actions on FMLP receptors lagged priming of FMLP-induced degranulation. Moreover, TNF-alpha enhanced degranulation responses to leukotriene B4 and platelet-activating factor but paradoxically down-regulated leukotriene B4 receptors and only transiently up-regulated platelet-activating factor receptors. Hence, TNF-alpha has pleiotropic effects on receptor expression; these effects diverge from priming; and a large part of the primed state must reflect enhancement of post-receptor events.
Rapid increases in the membrane expression of neutral endopeptidase (CD10), aminopeptidase N (CD13), tyrosine phosphatase (CD45), and Fc gamma-RIII (CD16) upon stimulation of human peripheral leukocytes with human C5a.
Authors: Werfel T , Sonntag G , Weber M H , Götze O 
Published: December 2022

Abstract
Rapid increases in the membrane expression of C3 receptors on granulocytes and monocytes in response to the anaphylatoxin C5a have previously been described. In this study we demonstrate increases in the membrane expression of neutral endopeptidase (NEP, CD10, CALLA), aminopeptidase N (APN, CD13), tyrosine phosphatase (CD45/CD45Ro) and the Fc R Fc gamma-RIII (CD16) on granulocytes within minutes of treatment with human C5a. Monocytes responded to C5a with increases in CD13 and CD45/CD45Ro. These membrane modulations could be prevented by preincubating the C5a preparations with anti-C5a mAb C17/5 but not by pretreating the cells with cycloheximide. Increases of CD10, CD13, and CD11b but not CD11a (LFA-1) were also observed in leukocytes from patients undergoing hemodialysis with cuprophan membranes. The increase of CD16 on granulocytes was dependent on the presence of plasma during in vitro activation with C5a indicating that plasma contains inhibitors which prevent the previously described loss of Fc gamma-RIII upon stimulation of the cells.
Treatment of mice bearing BCL1 lymphoma with bispecific antibodies.
Authors: Brissinck J , Demanet C , Moser M , Leo O , Thielemans K 
Published: December 2022

Abstract
Bispecific antibodies with specificity for the CD3/TCR complex of CTL and a target cell Ag can bridge both cell types and trigger cellular cytoxicity. We have produced bispecific antibodies, directed against the surface-expressed Id of the mouse BCL1 lymphoma and the mouse CD3 complex, by hybrid-hybridoma fusion. Two recombination Ig were purified to homogeneity: B1 X 7D6F, which is univalent for Id and CD3 binding and B1 X 7D6M, which is univalent for Id binding but has lost the CD3 binding because of association of the anti-CD3 H chain with the inappropriate L chain. In vitro studies indicate that bridging the TCR/CD3 complex of resting T cells with tumor IgM Id and the appropriate bispecific antibody induced proliferation and secretion of IL-2. Furthermore, in cytotoxicity assays using 51Cr-labeled tumor cells, preactivated T cells could be targeted with the bispecific antibody to give complete lysis of the Ag+ tumor. Finally, the activity of the bispecific antibody was confirmed in vivo. Animals treated i.v. with 5 micrograms of bispecific antibody 9 days after receiving BCL1 cells were cured. Furthermore, when these animals were checked at 150 days for dormant or variant tumors, as have been reported after other forms of immunotherapy in this model, none could be found. Immunotherapy experiments comparing a mixture of control antibodies with the bispecific antibody demonstrate that tumor cell-T cell bridging is established in vivo and is required for therapeutic success. These results indicate the importance of bispecific antibodies as a novel form of treatment for cancer.
Prolonged expression of high molecular mass CD45RA isoform during the differentiation of human progenitor thymocytes to CD3+ cells in vitro.
Authors: Deans J P , Wilkins J A , Caixia S , Pruski E , Pilarski L M 
Published: December 2022

Abstract
CD45, the leukocyte common Ag, has been shown to characterize T cell development both within the thymus and among peripheral T cells. The work reported here demonstrates that human multinegative (MN) thymocytes, depleted of cells bearing CD3, CD4, CD8, and CD19, express predominantly the high molecular mass CD45RA isoform, and lack low molecular mass CD45RB isoforms and CD45R0 as detected by immunofluorescence. By immunoprecipitation of surface-labeled CD45 molecules from MN thymocytes, a proportion of the CD45 is in fact of low molecular mass but does not include epitopes recognized by CD45R0, nor by CD45RB mAb specific for the p190. This suggests either glycosylation variants of CD45RB/CD45R0 undetectable by our mAb, or underglycosylated CD45RA. MN thymocytes lack TCR-alpha beta mRNA confirming their early developmental stage. Upon culture with IL-2 or with mitogenic combinations of anti-CD2/CD28 mAb, MN thymocytes differentiate to acquire CD3, TCR-alpha beta, and in some cases CD4 and/or CD8. We have predicted that maintenance of CD45RA and lack of CD45R0 expression is fundamental to generative thymic development. If correct, this demands that unlike peripheral T cells, differentiation of MN thymocytes should be accompanied by prolonged expression of high molecular mass CD45 isoforms. Analysis of CD45 isoform expression during MN thymocyte development confirms this prediction and indicates that expression of CD45RA is maintained, at increasing density, for at least 8 to 12 days of culture. Unlike peripheral blood T cells, this is accompanied by the gradual acquisition of firstly the p190 isoforms of CD45RB and later by CD45R0, resulting in a population of CD3+TCR-alpha beta cells coexpressing CD45RA/RBp190/R0. Dot blot analysis of mRNA from differentiating MN thymocytes indicates prolonged expression of mRNA encoding CD45 exons a, b, and c, again in contrast to peripheral T cells which lose all mRNA for alternatively spliced CD45 exons within the first 24 h poststimulation. This is discussed in the context of negative selection during thymic development and interconversion of T cell subsets.
In vivo induction of cytotoxic T cell response by a free synthetic peptide requires CD4+ T cell help.
Authors: Fayolle C , Deriaud E , Leclerc C 
Published: December 2022

Abstract
Most attempts to induce CTL responses by in vivo priming with free synthetic peptides have been unsuccessful so far. However, two separate studies have recently succeeded in inducing antiviral CTL responses by immunizing mice with unmodified free synthetic peptides derived from nucleoproteins from either lymphocytic choriomeningitis virus or Sendai virus. In the present study, we have analyzed the cellular mechanisms by which the lymphocytic choriomeningitis virus synthetic peptide induced CTL responses. We demonstrated that this peptide, which was previously shown to be recognized by CD8+ T cells, also contains a helper CD4+ T cell epitope. It stimulates in vivo both CD4+ T cell-mediated CTL response. The in vivo elimination of CD4+ T cells by treatment with a mAb was shown to strongly reduce the antipeptide CTL response. This study therefore demonstrates that to be able to induce CTL responses, a peptide has to stimulate both CD4+ and CD8+ T cell subset.
A recombinant C-terminal fragment of staphylococcal enterotoxin A binds to human MHC class II products but does not activate T cells.
Authors: Hedlund G , Dohlsten M , Herrmann T , Buell G , Lando P A , Segrén S , Schrimsher J , MacDonald H R , Sjögren H O , Kalland T 
Published: December 2022

Abstract
Binding of staphylococcal enterotoxin A (SEA) to MHC class II encoded proteins is a prerequisite for its subsequent activation of a large fraction of T lymphocytes through interaction with variable segments of the TCR-beta chain. We cloned SEA in Escherichia coli and produced four recombinant fragments covering both the N- and C-terminal regions. These fragments were used to analyze the interaction between SEA and the human MHC class II products. A C-terminal fragment of SEA, representing amino acids 107-233 bound to HLA-DR and HLA-DP but did not activate T cells. The three other fragments (amino acids 1-125, 1-179 and 126-233) neither bound to MHC class II Ag nor activated T cells. SEA apparently bind to HLA-DR and HLA-DP through its C-terminal part, whereas T cell activation is dependent on additional parts of the protein.
Chemically modified antigen-presenting cells induce T lymphocyte allospecific hyporesponsiveness.
Authors: Ibrahim M A , Coode W K , Takei F , Ellis J S , Chain B M , Katz D R 
Published: December 2022

Abstract
We have investigated the interaction between murine T lymphocytes and allogeneic APC in an in vitro proliferative mixed leukocyte reaction. Our results demonstrate that freshly isolated potentially alloreactive murine splenic T lymphocytes, in primary culture, can be induced to develop a state of allospecific proliferative hyporesponsiveness in vitro by exposure to 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide-modified allogeneic APC, a method similar to that previously used to induce nonresponsiveness in murine Ag-specific self-MHC-restricted T lymphocyte clones. This hyporesponsiveness was: specific for the allohaplotype of inducing APC, maintained for 96 h in vitro, not due to cellular inhibitory mechanisms, and associated with reduced ability to secrete IL-2 but not IL-3. Induction of this hyporesponsiveness was not due to altered expression of class II MHC gene products on the APC but was associated with markedly reduced T lymphocyte-APC adhesive interactions despite the lack of a detectable immunophenotypic change in lymphocyte function-associated Ag 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) expression on the modified APC. Therefore, we propose that TCR occupancy in the absence of normal T lymphocyte-APC adhesive clustering may induce T lymphocyte tolerance.
Induction of in vivo hyporesponsiveness to contact allergens by hapten-modified Ia+ keratinocytes.
Authors: Gaspari A A , Katz S I 
Published: December 2022

Abstract
Because our previous in vitro studies of hapten-modified Ia+ keratinocytes (KC) indicated that these cells induced anergy in Ag-specific Th1 cells, we assayed such cells for their ability to induce unresponsiveness in an in vivo animal model system of delayed type hypersensitivity (allergic contact dermatitis). Naive animals that were treated with i.p. injections of FITC-modified Ia+ cultured Langerhans cells (cLC) developed allergic contact dermatitis to subsequent hapten challenge; whereas, animals treated with similar doses of FITC-Ia+ KC failed to become sensitized to epicutaneous application of FITC, as evidenced by absent ear swelling responses to a FITC challenge. Those animals that were first treated with intraperitoneal injections of hapten modified Ia+ KC could not be sensitized when they were subsequently exposed to sensitizing doses of FITC; whereas a similar first exposure to FITC-cultured Langerhans cells did not interfere with epicutaneous sensitization. This hyporesponsiveness to sensitization was hapten specific, as FITC-Ia+ KC-treated animals were hyporesponsive only to FITC but not to the irrelevant hapten, TNCB. Additionally, Ia- KC failed to induce unresponsiveness. Additional studies indicate that the hyporesponsiveness was not passively transferrable with splenocytes and was not related to the I-J MHC locus. In contrast to our in vitro studies, the unresponsiveness induced by hapten-modified Ia+ KC in vivo was transient in nature. These data indicate that hapten-modified Ia+ KC function in vivo as nonstimulatory accessory cells, by generating down-regulatory signals that can interfere with the induction of contact hypersensitivity.
T cell receptor gamma and delta gene rearrangements in scid thymocytes. Similarity to those in normal thymocytes.
Authors: Kienker L J , Kuziel W A , Garni-Wagner B A , Kumar V , Tucker P W 
Published: December 2022

Abstract
The nature of TCR gamma and delta gene rearrangements in 4- to 6-week-old scid thymocytes was examined by using the polymerase chain reaction technique, cloning, and DNA sequencing. Analysis of 78 sequences indicates that TCR gamma and delta gene rearrangements in scid mice generally resemble those in thymocytes from normal young adult mice. V gamma 1, V gamma 2, and V gamma 5 rearrangements are heterogeneous, with extensive N region addition and nucleotide excision from the recombining coding segments. In addition, homogeneous and fetal-like V gamma 3, V gamma 4, and V delta 1 rearrangements are observed. These rearrangements are currently difficult to interpret but may be significant with respect to whether certain homogeneous joints in normal mice are due to cellular selection or to the rearrangement process. scid TCR gamma and delta gene nucleotide sequences also reveal direct V-J delta joining, inter-(V-J-C gamma) cluster joining, and the possibility of inversional rearrangement at the gamma locus. Short sequence homologies may contribute to V(D)J recombination and to the rescue of blocked coding joints.
Expression of protein kinase C isoenzymes in thymocyte subpopulations and their differential regulation.
Authors: Freire-Moar J , Cherwinski H , Hwang F , Ransom J , Webb D 
Published: December 2022

Abstract
The expression of the different protein kinase C (PKC) isozymes in mouse thymocytes was studied to determine if there is a correlation between isozyme expression and thymocyte phenotype. Expression of PKC isozymes in thymocyte subsets (distinguished by the CD4 or CD8 Ag) was determined by message amplification phenotyping. The expression of mRNA for PKC-alpha, -beta, -epsilon, and -zeta, but not -gamma or -delta isozymes, was detected in all of the unstimulated thymocyte subpopulations analyzed. Thus no differences in the pattern of PKC isozyme expression were found that could be correlated with thymocyte phenotype. However, it was noted that the levels of PKC mRNA expression were affected by different stimuli in unfractionated thymocytes. Whereas mRNA levels of PKC-alpha and -beta were down-regulated by PMA and ionomycin treatment, no significant changes were seen in the levels of PKC-epsilon mRNA with these agents. PKC-epsilon mRNA decreased in thymocytes exposed to Con A similar to what has been reported for PKC-epsilon protein. PKC-zeta mRNA was also down-regulated by PMA or ionomycin, and the combination of both compounds caused a more rapid and drastic effect. Finally, PKC-delta mRNA expression was induced transiently in thymocytes only after exposure to PMA or Con A, and this induction was inhibited by ionomycin treatment. These results indicate that message levels of specific isoforms of PKC are uniquely regulated and suggest an additional level of control of PKC activity in activated lymphocytes.
Role of intrastructural/intermolecular help in immunization with peptide-phospholipid complexes.
Authors: Goodman-Snitkoff G , Good M F , Berzofsky J A , Mannino R J 
Published: December 2022

Abstract
The design of effective subunit vaccines requires the inclusion of both B and T cell epitopes. The best mechanism for including both types of epitopes within an Ag is dependent upon how the Ag is processed by the APC for presentation to a responsive Th cell. If it is more efficient to process a single molecule for both helper and primary epitopes, than covalent linkage of B cells and T cell epitopes for intramolecular presentation of help would be recommended. If however, separate peptides containing either B or Th cell epitopes could be included within a single complex for the elicitation of intermolecular/intrastructural help, more antigenically diverse structures could be designed. This paper reports that it is possible to generate intermolecular/intrastructural help within an antigenic peptide-phospholipid (PL) complex. These peptide-PL complexes use well defined epitopes from Plasmodium falciparum as Ag. In addition to generating intrastructural help, we have shown that the Ir to these peptide-PL complexes is controlled by Ir genes and is similar to the Ir to the circumsporozoite protein of this pathogen.