bluuebunny/crossref_metadata_2025_split huggingface dataset:
The common gamma-chain of cytokine receptors regulates intrathymic T cell development at multiple stages.
Authors: He Y W , Nakajima H , Leonard W J , Adkins B , Malek T R 
Published: December 2022

Abstract
Signaling through the common gamma chain (gamma c), a subunit of the receptors for IL-2, -4, -7, -9, and -15, is critical for lymphocyte development, with the IL-7/IL-7R representing one important interaction. To investigate the stages of intrathymic T cell development that are dependent on gamma c and to determine whether gamma c controls T cell development solely as a component of the IL-7R, intrathymic T cell development was compared in IL-7R alpha-deficient mice and anti-gamma c-treated chimeric mice reconstituted with bone marrow and purified pro-T cells. In the presence of anti-gamma c, each of four phenotypically distinguishable stages of CD4- CD8- thymocytes failed to reconstitute T cell development, suggesting that each of these subsets of pro-T cells required gamma c for their differentiation and/or growth. Reconstitution of anti-gamma c-treated chimeric mice with bone marrow from IL-7R alpha-deficient mice indicated that IL-7R only partially contributed to intrathymic T cell development. Furthermore, when compared with IL-7R-deficient mice, anti-gamma c chimeric and gamma c-deficient mice exhibited a distinct phenotypic pattern of pro-T cell development. Collectively, these results indicate that several gamma c-sharing cytokines may contribute to T cell development in the thymus and suggest that one of these cytokines may be novel.
Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death.
Authors: Hurtado J C , Kim Y J , Kwon B S 
Published: December 2022

Abstract
Previously, we and others showed that signals relayed through the murine T cell Ag 4-1BB enhance primary T cell responses, and that blocking the interaction of 4-1BB with its ligand results in decreased responses to polyclonal activators and to alloantigens. Because 4-1BB expression is induced following primary stimulation, we investigated the role of signaling through this molecule in the reactivation of proliferating T cells. To this end, preactivated, 4-1BB-expressing T cells were restimulated in the presence of plate-immobilized mAbs directed against 4-1BB or the prototypic costimulatory molecule CD28. In this work, we show that in the presence of either signal, T cells respond to TCR cross-linking with strong proliferative responses and cytokine production; moreover, our findings indicate that T cell proliferation partially correlates with surface 4-1BB expression. In addition, our results suggest that Ab-mediated costimulatory signals can act independently of potential accessory B7-CD28/CTLA-4 (cytotoxic T lymphocyte Ag-4) interactions. Importantly, the characteristic DNA fragmentation and apoptotic cell death observed after TCR re-engagement are inhibited comparably in the presence of either 4-1BB or CD28 signaling.
Induction of IL-15 messenger RNA and protein in human blood-derived dendritic cells: a role for IL-15 in attraction of T cells.
Authors: Jonuleit H , Wiedemann K , Müller G , Degwert J , Hoppe U , Knop J , Enk A H 
Published: December 2022

Abstract
IL-15 is a pleiotropic cytokine with IL-2-like functions. As IL-15 was shown to be mitogenic for T cells, we wondered whether human blood-derived dendritic cells (DC), as the primary stimulators of T cell responses, are able to produce IL-15. To test our hypothesis, DC were grown under serum-free conditions from human peripheral blood using granulocyte-macrophage CSF and IL-4. Cultures were assayed for IL-15 mRNA production at various times by semiquantitative reverse transcription-PCR. Low baseline signals were detected from days 0 to 5 of culture. A significant increase was detected from days 5 to 9 of the culture. When DC were further enriched by immunomagnetic beads to &gt;98% purity as determined by CD83 staining, IL-15 mRNA signals were exclusively found in the CD83+ fraction. This increase in mRNA signals was paralleled by IL-15 protein release from days 9 to 12 as detected by CTLL-2 assay and ELISA. In addition, protein levels were increased &gt;10-fold by adding paramagnetic beads to the cultures, thereby inducing phagocytic activity. Furthermore, DC supernatants were tested for chemokinetic and chemotactic activities for T cells in a checkerboard filter assay. It was shown that supernatants express chemokinetic and chemotactic activity for T cells. This activity was blocked almost completely by addition of an anti-IL-15 mAb. Our data show that human blood DC contain IL-15 mRNA and produce functional protein that is induced in culture. Protein release is triggered by phagocytic activity. Furthermore, DC-derived IL-15 has chemotactic and chemokinetic activities for T cells, suggesting a role for IL-15 as an attractant of T cells during the initial DC/T cell interaction.
Roles of IL-4 and IFN-gamma in stabilizing the T helper cell type 1 and 2 phenotype.
Authors: Nakamura T , Lee R K , Nam S Y , Podack E R , Bottomly K , Flavell R A 
Published: December 2022

Abstract
It has previously been reported that Th1 CD4 T cell populations can be converted to IL-4 producers, whereas Th2 populations are refractory to IL-12-mediated IFN-gamma production. We have recently shown that CD30 is a marker for the IL-4 response and have therefore used CD30 here to study Th1 and Th2 commitment. We show that Th2 cell populations normally show a stable phenotype and fail to respond to IL-12 because of endogenous IL-4 production. IFN-gamma abrogates this antagonistic effect of IL-4 and permits the conversion of Th2 populations to IFN-gamma producers by IL-12. In the complete absence of IL-4, however, IFN-gamma is not required for this transformation, and Th1 cells generated by IL-12 become committed to the Th1 pathway and lose the ability to respond to IL-4. Thus, the balance between local IL-4 and IFN-gamma in an immune response is a key factor in determining the outcome of the CD4 effector T cell response.
Presentation on class II MHC molecules of endogenous lysozyme targeted to the endocytic pathway.
Authors: Parra-López C A , Lindner R , Vidavsky I , Gross M , Unanue E R 
Published: December 2022

Abstract
We compared the processing and presentation of the model Ag, hen-egg white lysozyme (HEL) expressed in C3.F6 APC as a fusion protein to three different acid hydrolases: cathepsin D, to an unglycosylated form of cathepsin D, and to pepsinogen. As expected from the biology of mannose 6-phosphate (Man-6-P)-containing enzyme, cathepsin D-HEL was delivered to the endosomal/lysosomal system. In contrast, the unglycosylated cathepsin D-HEL was retained in ER/Golgi and some was found in lysosomes. Most of pepsinogen-HEL was rapidly secreted from the APC. All transfectants presented HEL epitopes to T cell hybridomas. Regardless of the main route of traffic of the proteins, the strong I-Ak binding epitope HEL 48-62 was well presented by all. The biochemical forms of this epitope were identical for all. Three other epitopes of HEL that bind I-Ak with less affinity were processed equally well by unglycosylated cathepsin D-HEL and HEL-Ld. The glycosylated cathepsin D-HEL was less efficient in generating the 114-129 epitope. Pepsinogen-HEL was the less efficient of all transfectants in presenting these subdominant epitopes. Soluble cathepsin D-HEL recovered from culture supernatant was strongly immunogenic when added to C3.F6. The uptake was inhibited by free Man-6-P, indicating that the surface Man-6-P receptor can effectively deliver proteins to the class II MHC system.
Induction of alloantigen-specific T cell tolerance through the treatment of human T lymphocytes with wortmannin.
Authors: Taub D D , Murphy W J , Asai O , Fenton R G , Peltz G , Key M L , Turcovski-Corrales S , Longo D L 
Published: December 2022

Abstract
Signaling through the CD28 molecule on T cells by its natural ligand, B7, on APCs has recently been shown to require the presence of an active phosphatidylinositol 3-kinase pathway to mediate some of its costimulatory activities (1-7). Using the phosphatidylinositol 3-kinase inhibitor, wortmannin (WN) (8), on human and murine T cells, we have inhibited B7-1-mediated T cell activation and induced Ag-specific tolerance. The addition of WN and/or the B7-1 antagonist, CTLA4Ig, to primary human T cell cultures stimulated with B7-1-transfected allogeneic melanoma cell lines inhibited the generation of alloantigen-specific proliferative and cytolytic responses in vitro. Subsequent examination of these WN- and CTLA4Ig-treated primary T cell cultures revealed that these lymphocyte populations were tolerized to rechallenge with the priming alloantigens in secondary cultures in the absence of additional inhibitor(s). However, reactivity to a third party allogeneic stimulator remained intact. This WN-induced tolerance was reversed by the addition of high dose IL-2, but not IL-4 or IL-7, to the primary cultures, indicating that T cell anergy, not deletion, was responsible for this phenomenon. In vivo studies using a murine graft-vs-host disease (GVHD) model demonstrated that WN treatment of allogeneic donor lymphocytes in vitro failed to generate a significant GVHD in irradiated mouse recipients compared with control allogeneic donor lymphocytes. These findings suggest potentially novel therapeutic strategies for the prevention of GVHD.
Transcriptional regulation of platelet-activating factor receptor gene in B lymphoblastoid Ramos cells by TGF-beta.
Authors: Yang H H , Pang J H , Hung R Y , Chau L Y 
Published: December 2022

Abstract
The expression of platelet-activating factor (PAF) receptor gene was up-regulated in a time- and dose-dependent manner in a B cell line (Ramos) following exposure to TGF-beta 2. The TGF-beta 2-induced increment of PAF receptor mRNA was at least partly due to an increase in transcriptional rate as demonstrated by nuclear run-off experiments. Transient transfection of cells with PAF receptor transcript I gene promoter fused to a luciferase reporter gene revealed that the TGF-beta-responsive element (T beta RE) lies between the sequence from -44 to -17 relative to the transcriptional start site. Insertion of the T beta RE upstream of the unresponsive minimal thymidine kinase promoter conferred the TGF-beta-inducibility. Gel mobility shift assay demonstrated the specific binding of nuclear factors to the T beta RE. The T beta RE binding activity was gradually increased and reached a maximum at 3 h and subsequently returned to basal level at 5 h in cells following TGF-beta 2-treatment. Concomitant treatment of cells with cycloheximide abolished the increases in both T beta RE-binding activity and expression of PAF receptor mRNA, indicating that de novo protein synthesis is required to exert TGF-beta 2 effect. Methylation interference analysis revealed that the T beta RE-binding protein recognized a purine-rich sequence, 5'-GGGGTG-3'. Point mutations of the consecutive guanine nucleotides significantly reduced the DNA-binding activity and the TGF-beta-induced promoter activity. Collectively, these results clearly demonstrate that a T beta RE proximal to the transcriptional initiation site of the human PAF receptor transcript I gene mediates the up-regulation of PAF receptor gene expression in Ramos cells by TGF-beta 2.
Alloreactive T cell recognition of MHC class I molecules: the T cell receptor interacts with limited regions of the MHC class I long alpha helices.
Authors: Smith K D , Lutz C T 
Published: December 2022

Abstract
T cells recognize MHC-bound peptide, suggesting that the TCR contacts surface MHC residues adjacent to bound peptide, but the extent of MHC contact is not known. T cells also may recognize peptide-induced conformational changes, and alloreactive T cells may recognize surface MHC structures in addition to or independent of bound peptide. Alloreactive T cells are not intentionally biased to recognize particular MHC-bound peptides and should reveal general constraints for TCR binding. To map TCR binding sites, we tested 60 HLA-B7 site-specific mutations with 12 alloreactive CTL clones that express different TCRs. The alloreactive CTL clones recognize solvent-accessible residues that cluster between positions 62 to 80 and 150 to 170. Thus, TCRs contact largely overlapping MHC structures in the alpha1 and alpha2 domain long alpha helices. The dimensions and location of this site are consistent with recently reported crystallographic studies of two TCR/peptide-MHC class I complexes. In contrast to TCR, Abs recognize multiple discrete epitopes that encircle the peptide binding groove and potentially encompass the entire surface of the MHC molecule. Our data suggest that TCRs dock with a common discrete MHC site and that recent crystallographic models are likely to be generally applicable to T cell recognition of peptide-MHC class I complexes.
CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice.
Authors: Chatenoud L , Primo J , Bach J F 
Published: December 2022

Abstract
Low doses of the CD3 mAb 145 2C11 restored self tolerance to beta cell Ags in adult overtly diabetic NOD mice. Within 2 to 4 wk after treatment, complete and permanent remission of diabetes was observed. Autoreactive T cells were not deleted in CD3 Ab-protected animals as evidenced first, by the persistence of peripheral insulitis and, second, by the capacity of spleen cells from CD3 Ab-treated mice to transfer diabetes to adult irradiated syngeneic recipients. Moreover, the conferred tolerance was reproducibly reversed by a single injection of cyclophosphamide. For 5 to 7 wk after treatment, IFN-gamma production by stimulated spleen cells was significantly decreased in treated animals. One unique feature was that the CD3 Ab-induced tolerance ensued only from treatment of overtly diabetic NOD mice. Durable protection was exclusively observed when treating mice with recent onset disease (14-20 wk old). At variance with this finding, treatment of 4- and 8-wk-old mice was without effect, and complete but transient protection followed the treatment of 12-wk-old NOD mice. The tolerogenic properties of 145 2C11 did not depend on its mitogenic capacity, since nonmitogenic F(ab')2 fragments also appeared potent at inducing durable remission in overtly diabetic NOD, although nonmitogenic CD3 F(ab')2 fragments could mediate T cell signaling, as evidenced by cytokine gene transcription (IL-2, IFN-gamma, IL-4, and IL-10) assessed by PCR on splenocytes from treated mice. A concomitant cyclosporine treatment abrogated the CD3 mAb-induced protection, further pointing to the crucial role of T cell signaling in the effect observed.
Studies in Isohemagglutination
Authors: Parr Leland W. 
Published: December 2022

Summary Of Results
Data for Armenians, Arabic Moslems and Arabic Christians are given making it possible to assign these groups their racial indices. It is to be noted that Arabic Moslems and Arabic Christians, speaking the same language, living the same life, and locally thought to be the same people, yield significantly different values.
The value of this method of approach to racial relationships is questioned.
Preliminary data are presented for the Druzes and the Metwallis, both of which groups derive from the Moslems. Further work will have to be done before these groups can be either identified with or set definitely apart from the Moslem Arab.
A new family in which both father and mother belong to group AB is presented. No evidence is offered from this family or from one other, where one parent is AB, which will enable us to choose the three multiple allelomorphs theory over that of two independent pairs of factors hypothesis, but the accumulating evidence favors the former.
Studies in Isohemagglutination
Authors: Wiener Alexander S. , Lederer Max , Polayes S. H. 
Published: December 2022

Summary
Of all the theories on the heredity of blood groups that have been presented up to the present time, Bernstein's theory is most satisfactory. Apparent exceptions to this theory are due to: (a) faulty technique; (b) failure to test a sufficient number of people; (c) errors in computation; (d) failure to study a homogeneous group, and (e) selection of a subgroup for study which is not representative of the entire group.
Quantitative Studies on the Action of Compound Hemolysins
Authors: Gahl Rudolf 
Published: December 2022

Summary
A quantitative study of the characteristic curves defined in preceding papers (1, 2 and 3) led to the conclusion that the complexities of these curves as they are experimentally obtained can be removed and the curves so simplified that they assume forms which are in harmony with the views proposed by Svante Arrhenius on the reaction between hemolytic amboceptor and complement by introducing the assumption into the calculation that neither heat inactivated hemolytic amboceptor serum is free from complement nor complement serum from natural amboceptor.
Geometrical methods for introducing suitable corrections were developed for this purpose.
The application of such methods permits the quantitative estimation of the contaminations.
Heat inactivated hemolytic amboceptor serum may, when undiluted, contain complement in quantities not much lower in order of magnitude than the complement serum. Its effect may nevertheless not be noticeable on the Wassermann reaction as long as potent amboceptor serum is used which permits a correspondingly high dilution.
Application of the law of chemical mass action makes the construction of theoretical systems of characteristic curves possible. Only the exponents of the mass law equations determine the shape of these curves. Such curve systems were calculated under various assumptions regarding the chemical combination between amboceptor and complement and found to present typical pictures characteristic of each reaction.
It was shown that when the corrections above referred to are applied to the curves derived from the law of chemical mass action in the opposite direction complex curves result which agree with those experimentally obtained within the limits of experimental errors except in the region of complement deviation which the theory is not designed to cover.
Rational systems for expressing strength of amboceptor and complement were proposed.
Conclusions were drawn regarding the relative molar concentrations of amboceptor and complement.
The assumption of a stoichiometric chemical reaction between amboceptor and complement explains all observations. The stipulation of an enzymatic nature of one or both does not seem justified.
Summing up the results of all four papers on this subject, we might state that while Manwaring rightfully pointed out that Arrhenius' mathematical representation of the reaction between hemolytic amboceptor, complement and red blood cells is not in agreement with the experimental facts, we find it in agreement with them so far as only the reaction between amboceptor and complement is concerned. The constants which Arrhenius used in his equations are as all constants obtained by experiment subject to revision by later investigators.
The Skin Reaction in the Sensitized Guinea Pig
Authors: Ramsdell Susan Griffith 
Published: December 2022

Summary
Guinea pigs actively sensitized and skin-tested, using trypan blue as a technical aid, gave reactions to the antigen-serum in dilutions as high as 1:10,000. Passive sensitization of the skin of a normal animal could be demonstrated as early as the sixth day after treatment of the actively sensitized animal, and was regularly more consistent than the test for passive sensitization by shock. Whether the antibody responsible for the skin reaction is a separate one from the anaphylactic antibody or merely an extension of its manifestation is not clear.
Creating CTL Targets with Epitope-Linked β2-Microglobulin Constructs
Authors: Uger Robert A. , Barber Brian H. 
Published: December 2022

AbstractEliciting a strong CTL response is dependent upon displaying suitably high levels of specific class I MHC/peptide complexes at the cell surface. In an effort to enhance the presentation of defined CTL target structures, two unique peptide-linked β2-microglobulin (β2m) molecules were constructed. The first, designated NP(366–374)-L8-hβ2m, links the carboxyl terminus of the H-2Db-restricted influenza nucleoprotein (NP) epitope NP366–374 to the amino terminus of hβ2m through an eight-amino acid glycine/serine linker. The second molecule, designated NP(147–155)-L12-hβ2m, similarly couples the H-2Kd-restricted influenza NP epitope NP147–155 to hβ2m via a 12-residue polypeptide linker. Transfection of the NP(366–374)-L8-hβ2m vector into H-2b-expressing cell lines sensitized these cells for lysis by NP366–374-specific CTLs. Free NP peptide could not be detected when class I bound peptides were acid-extracted from the surface of NP(366–374)-L8-hβ2m transfectants, indicating that CTL killing was mediated by recognition of the peptide linked to hβ2m and not by a degradation by-product. CTL target structure formation was also achieved by an exogenous presentation pathway. H-2d-expressing target cells were sensitized for lysis when pulsed with NP(147–155)-L12-hβ2m protein derived from an Escherichia coli cell lysate. The effect of recombinant NP(147–155)-L12-hβ2m was inhibited by competitor wild-type hβ2m, indicating that the active peptide-hβ2m fusion protein remained intact. The observation that β2m with covalently attached peptide can effectively create CTL target structures in vitro offers new possibilities for the in vivo induction of epitope-specific CTL responses by either DNA immunization or injection of the purified epitope-linked β2m.
Amastigote Surface Proteins ofTrypanosoma cruziAre Targets for CD8+ CTL
Authors: Low Hoi Pang , Santos Maria A. M. , Wizel Benjamin , Tarleton Rick L. 
Published: December 2022

AbstractAmastigotes of Trypanosoma cruzi express surface proteins that, when released into the host cell cytoplasm, are processed and presented on the surface of infected cells in the context of MHC class I molecules to be recognized by CD8+ CTL. To further understand the role of CTL in T. cruzi infection, we used the available MHC class I peptide binding motifs to identify potential CTL target epitopes in two recently described T. cruzi amastigote surface proteins, ASP-1 and ASP-2. The predicted amino acid sequences of ASP-1 and ASP-2 were screened for H-2b allele-specific class I peptide motifs, and four peptides (PA11, PA12, PA13, and PA14) and six peptides (PA5, PA6, PA7, PA8, PA9, and PA10) were synthesized from ASP-1 and ASP-2, respectively. The majority of the peptides bound to some degree to H-2b class I MHC molecules, and six of 10 of the peptides stimulated spleen cells from T. cruzi-infected mice to lyse target cells sensitized with the homologous peptides. Short term T cell lines specific for three of these peptides also lysed T. cruzi-infected target cells. These results demonstrate that ASP-1 and ASP-2 are targets of in vivo generated CTLs and that this CTL response induced by T. cruzi infection is parasite and peptide specific, MHC restricted, and CD8 dependent.