bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced cytotoxicity of IFN-gamma-producing CD4+ cytotoxic T lymphocytes specific for T. gondii-infected human melanoma cells.
Authors: Yang T H , Aosai F , Norose K , Ueda M , Yano A 
Published: December 2022

Abstract
CD4+ lines specific for Toxoplasma gondii-infected human melanoma P36 cells were established from PBL of a patient with chronic toxoplasmosis. CD4+ CTL lines were obtained by weekly in vitro stimulation with T. gondii-infected P36 cells that shared HLA-DR4 molecules with the patient. The lytic activity of CD4+ CTL lines against T. gondii-infected P36 or T. gondii-infected autologous EBV-transformed B lymphoma (EBV-Ya) was inhibited by anti-HLA-DR mAb, whereas anti-HLA-A, B, C mAb failed to block the lytic activity. Thus, the cytotoxicity of CD4+ CTL lines against T. gondii-infected P36 was restricted by HLA-DR molecules. In response to Ag-specific stimulation, CD4+ CTL lines produced significant levels of IFN-gamma. Exogenously added IFN-gamma up-regulated the surface expression of MHC class II, but not of class I in T. gondii-infected P36 cells. In addition, the CTL activity against T. gondii-infected P36 cells was augmented when target cells were co-cultured with IFN-gamma. These data indicate that CD4+ CTL-mediated cytotoxicity against T. gondii-infected melanocytes is enhanced by the autocrine production of IFN-gamma. Further, CD4+ CTL may play a role in the manifestation of toxoplasmic retinochoroiditis by killing T. gondii-infected melanocytes.
Experimental autoimmune encephalomyelitis-resistant mice have highly encephalitogenic myelin basic protein (MBP)-specific T cell clones that recognize a MBP peptide with high affinity for MHC class II.
Authors: Abromson-Leeman S , Alexander J , Bronson R , Carroll J , Southwood S , Dorf M 
Published: December 2022

Abstract
BALB/c mice are resistant to disease induction when experimental protocols that induce experimental autoimmune encephalomyelitis (EAE) in susceptible strains of animals are used. We have previously described a panel of myelin basic protein (MBP)-specific CD4+ T cell clones from BALB/c mice, two of which induce moderate EAE when transferred to syngeneic recipients. These clones are I-E(d) restricted and recognize residues 151-160 of mouse MBP. Here, we describe a series of 17 MBP-reactive T cell clones, which were derived from two BALB/c mice. All are I-A(d) restricted and recognize nested epitopes in peptide 59-76 of mouse MBP. Four different TCR V beta chains are used by this panel of clones; these include V beta 8.2 (10/17), V beta 8.1 (2/17), V beta 7 (3/17), and V beta 14 (2/17). Twelve of fourteen clones tested adoptively transferred severe demyelinating EAE to syngeneic recipients. Studies of relative binding affinities of MBP peptides to class II molecules I-A(d) and I-E(d) show that peptide 59-76 binds with extremely high affinity to I-A(d), whereas three peptides that contains residues 151-160 bind poorly to I-E(d). These results are consistent with a growing number of reports that show that high affinity binding to class II is required for autoantigenic stimulation. Despite encephalitogenicity of 59-76-reactive T cells, active immunization of BALB/c mice with peptide 59-76 in adjuvant failed to induce either clinical or histologic signs of EAE. The implications of these findings for mechanisms of genetically determined EAE resistance are discussed.
Induction of peptide-specific CD8+ CTL clones in beta 2-microglobulin-deficient mice.
Authors: Cook J R , Solheim J C , Connolly J M , Hansen T H 
Published: December 2022

Abstract
We have examined the ability of beta 2-m- mice to produce CD4-8+ T cells by generating CD8+ CTLs to a defined ligand. We report here the first demonstration of peptide-specific, self-class I MHC-restricted CTLs from beta 2-m-deficient mice. We have used the KOD mouse, an H-2d beta 2-m- strain, to generate CTLs that recognize the class I MHC molecule Ld in association with one of two Ld-binding immunogenic peptides. Testing of these CTLs on a panel of Ld-binding peptides reveals a high degree of peptide specificity. Peptide-specific CTL bulk cultures from KOD mice differ from those generated in beta 2-m+ mice in that they possess altered affinities for their peptide ligands. In addition, we show that CTLs generated from beta 2-m- mice in the presence of beta 2-m+ stimulator cells and exogenous peptide are specific either for the exogenous peptide or for endogenous peptides that are present in association with Ld on the surface of beta 2-m+ cells, but are not present at detectable levels on beta 2-m- cells. These results demonstrate that positive selection of CD8+ CTLs can occur in vivo on the very low levels of class I MHC found in the KOD mouse. Furthermore, CTLs from the KOD mouse maintain a high degree of peptide specificity despite reduced levels of class I MHC.
Generation of T cells with differential responses to alloantigens in CD45 exon 6-deficient mice.
Authors: Kong Y Y , Kishihara K , Yoshida H , Mak T W , Nomoto K 
Published: December 2022

Abstract
We characterized the CD45+ population in the CD45 exon 6-deficient mice and addressed a question as to whether the T cells keep responsive properties to alloantigens. The peripheral CD45+ T cells from the untreated knockout mice showed a decreased expression level of CD45 but increased expression levels of LFA-1 alpha and CD44, indicating that the T cells are possibly in an activation state. The CD45 exon 6-deficient mice could readily reject fully allogeneic skin grafts but not non-MHC-disparate skin grafts. The skin allograft-rejected CD45 exon 6-deficient mice showed an increased number of peripheral CD8+ T cells expressing an isoform of CD45RB (CD45 zeta). In vitro assays including mixed lymphocyte reaction, CTL, and cytokine productions were consistent to the in vivo results. Furthermore, the effector cells shown in these assays were CD45+CD8+ T cells expressing a CD45RB isoform, CD45 zeta. Moreover, the CD45+ T cells had an abnormal regulation of CD45 expression level, as they could not increase their CD45 expression level after in vitro allogeneic stimulation. These results indicate that abnormal mature T cells in the periphery of CD45 exon 6-deficient mice cannot respond to nominal Ags presented by MHC but can react to allo-MHC. The reason that such functionally impaired T cells can be generated in the mice is still unknown but these results imply that there is differential requirement of CD45 function for alloreactive T cells in a thymic selection(s) and in effector functions.
Temporal loss of the activated L-selectin-low phenotype for virus-specific CD8+ memory T cells.
Authors: Tripp R A , Hou S , Doherty P C 
Published: December 2022

Abstract
Whether the L-selectin-low (L-sel-lo) phenotype of acutely stimulated CD8+ T cells is a permanent characteristic of long-term memory CTL precursors (p) is addressed for mice primed with an influenza A virus or the murine parainfluenza type 1 virus, Sendai virus. In both cases, many of the splenic CD8+ CTLp gradually lose the predominantly L-sel-lo profile associated with recently generated CTLp populations. The influenza-specific CTLp also tend to revert from the activated alpha 4-integrin-high to the resting alpha 4-integrin-low form. The kinetics of the switch back to the "naive" L-sel-hi phenotype differs for the influenza and Sendai virus models, perhaps reflecting events occurring during the acute phases of these responses. The return to being L-sel-hi is not due to irreversible lymphocyte senescence, because restimulation of this set with the inducing virus in vitro causes most of the cells to become L-sel-lo. Also, despite the time-related drift of these particular memory CTLp to the L-sel-hi state, the size of the total pool of L-sel-lo CD8+ T cells increases with age.
Sequence analysis of the gene for a novel superantigen produced by Yersinia pseudotuberculosis and expression of the recombinant protein.
Authors: Ito Y , Abe J , Yoshino K , Takeda T , Kohsaka T 
Published: December 2022

Abstract
We previously reported that the Gram-negative bacterium Yersinia pseudotuberculosis produces a superantigen (YPM, Y. pseudotuberculosis-derived mitogen) that expands T cells bearing V betas 3, 9, 13.1, and 13.2 in an MHC class II-dependent manner. Based on the previously determined N-terminal 23 amino acids of YPM (T-D-Y-D-N-T-L-N-S-I-P-S-L-R-I-P-N-I-A-T-Y-T-G- (one-letter code)), we cloned the ypm gene and analyzed the nucleotide sequence. The gene encodes a 151-amino acid protein with a 20-amino acid signal peptide at its N terminus. The recombinant YPM expressed by the cloned gene exerted a mitogenic activity on human PBMC at a concentration of approximately 1 pg/ml. T cells bearing V beta 13.3 were preferentially expanded as well as T cells bearing the same V beta repertoires stimulated by native YPM. T cells were stimulated by the recombinant YPM in the presence of either fixed or unfixed HLA class II-transfected mouse fibroblasts. Furthermore, sequence diversity in the junctional region of the TCR beta-chain containing the V beta 3 element could be observed after stimulation by the recombinant YPM. These results indicate that YPM belongs to the category of superantigens and should be included as a novel member. The amino acid sequence of the mature protein showed no significant homology to other superantigens derived from Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes. This observation, together with the substantially smaller m.w. suggest that ypm must have evolved from a different ancestral gene.
Self and foreign 60-kilodalton heat shock protein T cell epitope peptides serve as immunogenic carriers for a T cell-independent sugar antigen.
Authors: Könen-Waisman S , Fridkin M , Cohen I R 
Published: December 2022

Abstract
Healthy individuals manifest natural T cell reactivity to epitopes of the 60-kDa heat shock protein (hsp60) of both self and bacterial origin. The present studies were done to learn whether defined peptides of hsp60 could function as T cell carrier epitopes for a poorly immunogenic T-independent capsular polysaccharide, the Vi Ag of Salmonella typhi. Homologous peptides were synthesized from the mouse self-hsp60 molecule (CP1m), from the closely related human hsp60 molecule (CP1h), and from the more distant Escherichia coli (CP1ec) and mycobacterial (CP1mt) hsp60 molecules. The peptides were conjugated to Vi and tested for their immunogenicity in BALB/c (H-2d) and H-2 congenic mice (H-2k and H-2b). We now report that the self-CP1m and cross-reactive CP1h peptides were as immunogenic as was the non-cross-reactive foreign CP1ec peptide. Small amounts of the CP1 peptide, even in PBS, sufficed to induce anti-Vi Abs of the IgG1 (T-dependent) isotype in naive mice. The carrier effect was associated with the ability of the peptides to bind to APC and to induce T cell proliferation. H-2d and H-2k mice, but not H-2b mice responded to CP1m/h and CP1ec. None of the mice responded to CP1mt. No signs of inflammation or autoimmune disease were detected. Thus, natural T cell autoimmunity exists and can be harnessed to provide T cell help for Ab production to a foreign bacterial molecule in a synthetic vaccine.
Infection of IL-4-deficient mice with the parasitic nematode Brugia malayi demonstrates that host resistance is not dependent on a T helper 2-dominated immune response.
Authors: Lawrence R A , Allen J E , Gregory W F , Kopf M , Maizels R M 
Published: December 2022

Abstract
Resistance of intact mice to infection with the filarial nematode, Brugia malayi is dependent on the presence of T cells. To investigate the role of Th2 cells in this protection, mice with a targeted disruption of the IL-4 gene were infected with different developmental stages of B. malayi. We examined the phenotypic changes in the immune response and the survival of each stage in these mice. In wild-type mice, adult female worms induce Th2 responses, characterized by antigen-specific IgG1 production, elevated IgE, and marked IL-4 secretion by splenocytes stimulated in vitro with Brugia extract. However, first stage larvae (microfilariae), induce Th1 responses with the appearance of antigen-specific IgG2a, IgG2b, and IgG3 and IFN-gamma secretion by splenocytes. Infection of IL-4-deficient mice revealed a dramatic change in the response to adult worms, with a severe reduction in IgG1 production and a corresponding increase in the production of IgG2a, IgG2b, IgG3, and IFN-gamma release. The switch to Th1-type responses was particularly marked in IL-4-deficient recipients of female worms, which continually release live microfilariae. In the absence of IL-4, down-regulation of the microfilarial-induced Th1 response does not occur. Despite these profound alterations to the immune response in IL-4-deficient mice, survival of infective larvae, adult worms, or microfilariae in the peritoneal cavity was unaffected. In mice, therefore, the prominent Th2-type response elicited by filarial parasites may not be an essential component of the host protective immune response.
HIV-1 infection of human macrophages impairs phagocytosis and killing of Toxoplasma gondii.
Authors: Biggs B A , Hewish M , Kent S , Hayes K , Crowe S M 
Published: December 2022

Abstract
The susceptibility of patients with AIDS to certain opportunistic infections is due to defective cell-mediated immunity. The contribution of direct infection of macrophages with HIV-1 to this defect is unknown. To address this issue, we infected normal human monocyte-derived macrophages with a monocytotropic strain of HIV-1 and examined their ability to phagocytose and kill the opportunistic pathogen, Toxoplasma gondii. Phagocytosis of heat-killed T. gondii was reduced in HIV-infected macrophages compared with mock-infected controls. Opsonization of heat-killed T. gondii increased phagocytosis by both mock- and HIV-infected macrophages, but phagocytosis in HIV-infected cultures remained lower than in controls. Internalization of live T. gondii by macrophages was unaffected by HIV infection. Intracellular replication of live T. gondii was enhanced by HIV infection, as shown in four experiments, each using monocyte-derived macrophages from a different donor. Treatment of HIV-infected macrophages with IFN-gamma decreased parasite replication but not to control levels. These findings suggest that infection of macrophages by HIV may be a contributing factor to the reactivation of T. gondii infection in patients with AIDS.
High prevalence of serum IgA HIV-1 infection-enhancing antibodies in HIV-infected persons. Masking by IgG.
Authors: Kozlowski P A , Black K P , Shen L , Jackson S 
Published: December 2022

Abstract
IgA and IgG purified from sera of 20 HIV-infected persons were separately examined for ability to mediate Ab-dependent enhancement (ADE) of HIV-1 infection of U937 cells. Both isotypes were capable of enhancing infection of these cells. However, IgA from twice as many persons (14/20) displayed infection enhancement when compared with IgG. This activity was predominantly observed with IgA from asymptomatic HIV-seropositive subjects (9/9). Enhanced HIV infection by IgA was observed most often at concentrations equivalent to serum dilutions in the range 10(-3) to 10(-5) and could be inhibited by preincubation of U937 cells with a mAb specific for the Fc alpha receptor. Concentrations of IgG mediating ADE were generally present in sera at dilutions from 10(-4) to 10(-6). When IgG was adjusted to physiologic concentration and combined with an enhancing concentration of IgA, enhancement was not observed unless IgG was also present at a concentration which exhibited this activity. These results suggest that, in comparison with IgG, HIV-infected individuals more often produce IgA Abs reacting with enhancing determinants of HIV. IgA-mediated ADE of HIV infection may not play a significant role in facilitating systemic dissemination of HIV because of the presence of higher concentrations of IgG. However, the production of IgA HIV-enhancing Abs at mucosal sites, where fewer IgG plasma cells are present, could contribute to the pathogenesis of HIV infection and interfere with development of vaccines designed to induce HIV IgA Abs at mucosal surfaces.
Apparent split tolerance of CD8+ T cells from beta 2-microglobulin-deficient (beta 2m-/-) mice to syngeneic beta 2m+/+ cells.
Authors: Jhaver K G , Rao T D , Frey A B , Vukmanović S 
Published: December 2022

Abstract
beta 2-microglobulin-deficient (beta 2m-/-) mice express reduced levels of MHC class I molecules and, consequently, have impaired positive selection of CD8+ T lymphocytes in the thymus. However, small numbers of CD8+ CTLs can be found in beta 2m-/- mice after immunization with allogeneic as well as syngeneic beta 2m+/+ tumor or spleen cells. It has been proposed, therefore, that because of the low ligand density in beta 2m-/- mice, negative selection does not remove cells capable of recognizing syngeneic MHC class I expressed at normal levels. We report here that beta 2m-/- CD8+ T cells are partially tolerant to syngeneic beta 2m+/+ cells. Despite the ability of beta 2m-/- mice to raise CD8+ CTLs against syngeneic beta 2m+/+ cells, these CD8+ cells do not proliferate and do not secrete IFN-gamma or IL-3/granulocyte-macrophage-CSF upon in vitro stimulation with syngeneic beta 2m+/+ cells. In contrast, all of these cellular responses are displayed by the beta 2m-/- CD8+ cells upon recognition of the allogeneic MHC class I. These in vitro findings of partial responsiveness to syngeneic and of full responsiveness to allogeneic MHC class I correlate well with the ability of beta 2m-/- mice to reject allogeneic, but not syngeneic, tumors in vivo. It appears, thus, that the significantly reduced levels of MHC class I molecules found in beta 2m-/- mice, although not capable of inducing deletion of all reactive clones, can induce deletion of high affinity clones and, therefore, maintain tolerance to self-MHC class I, even when expressed at much higher (beta 2m+/+) levels.
Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated cdk4 homologue in normal human T lymphocytes.
Authors: Lucas J J , Szepesi A , Modiano J F , Domenico J , Gelfand E W 
Published: December 2022

Abstract
The PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), which shares extensive sequence homology (approximately 70%) with cdk4, was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12,13-dibutyrate and ionomycin (PDB/I) or PHA. The p40cdk6 protein was present in resting cells and increased amounts were detected 6 h after stimulation. It increased in amount throughout the first cell cycle but was present in reduced amounts at later times. Activity of the kinase, determined by in vitro phosphorylation of recombinant truncated retinoblastoma tumor suppressor gene (Rb) protein (p60Rb), paralleled p40cdk6 protein amounts. Cyclins D2 and D3 were the major cyclins associated with p40cdk6, with D2 predominating in early G1 phase. Both PDB and ionomycin were required for maximal accumulation of p40cdk6, but either agent alone stimulated some increase in amount and activity of the protein. p40cdk6 also increased in amount in cells activated in the presence of cyclosporin A or FK506, drugs that inhibit production of IL-2 and cell proliferation, suggesting that initial induction occurred independently of IL-2-mediated cell cycle progression. Furthermore, increased accumulation of p40cdk6 protein and activity occurred in cells rendered "competent" (responsive to IL-2) by a brief treatment with PDB/I. Thus, increased accumulation of the protein and its activity begin before IL-2/IL-2 receptor interaction, suggesting that the cdk6-cyclin D2 complex might be involved in acquisition of the competent state in human T lymphocytes.
Analysis of direct and inverted DJH rearrangements in a human Ig heavy chain transgenic minilocus.
Authors: Tuaillon N , Miller A B , Tucker P W , Capra J D 
Published: December 2022

Abstract
D to JH rearrangement can occur either by a deletional or an inversional mechanism. In this study, we have analyzed deletional and inversional D to JH recombination in a human Ig heavy chain transgenic minilocus. The analysis of these events in a transgenic minilocus rather than in vivo in the human is simplified by the presence of a limited number of well defined VH, D, and JH gene segments in the minilocus. We show that in the transgenic minilocus, all D gene segments can be rearranged by deletion and virtually all can be rearranged by inversion. We also show that depending upon the D gene segment, rearrangement by deletion occurs approximately 1 to 1000 times more frequently than rearrangement by inversion. Our data suggest that in vivo, signal and coding end sequences are the major influences on the rearrangement frequency of a particular gene segment in a given orientation rather than its position within the transgenic locus. Additionally, our data indicate that intronic and recombination signal sequences are involved in the bias for deletion over inversion rather than the recombinase machinery itself.
Platelet-activating factor directly stimulates in vitro migration of endothelial cells and promotes in vivo angiogenesis by a heparin-dependent mechanism.
Authors: Camussi G , Montrucchio G , Lupia E , De Martino A , Perona L , Arese M , Vercellone A , Toniolo A , Bussolino F 
Published: December 2022

Abstract
The aim of the present study was to investigate the angiogenic properties of platelet-activating factor (PAF). In vitro PAF was shown to induce a dose-dependent migration of human endothelial cells (EC) across the polycarbonate filters in Boyden's chambers. In contrast, D-PAF, the biologically inactive enantiomer, and Lyso-PAF did not stimulate a significant migration of EC. This effect of PAF was not associated with a proliferative response of EC to this mediator. Moreover, the ability of PAF to stimulate the migration of EC was independent of the presence of heparin in the medium. WEB 2170, a specific PAF receptor antagonist, prevented the migration of EC induced by PAF, thus suggesting a receptor-dependent stimulation. The expression of PAF receptor gene by EC was confirmed by reverse transcriptase-PCR and Southern blot analysis. The in vivo angiogenic effect of PAF was studied in mice using a model in which Matrigel was used for the delivery of mediators. PAF induced a dose-dependent angiogenic response, which at pharmacologic concentrations (1-5 microM) did not require heparin, but at physiologic concentrations (5-50 nM) required the presence of heparin at doses that were not angiogenic per se. The angiogenesis induced by 50 nM PAF was, indeed, inhibited both by protamine and by the PAF receptor antagonist WEB 2170. The angiogenic effect of D-PAF and Lyso-PAF was not significant. Neutralizing Abs to basic fibroblast growth factor induced a slight but not statistically significant reduction of the angiogenesis induced by PAF.