bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human microvascular endothelial cells.
Authors: Haraldsen G , Kvale D , Lien B , Farstad I N , Brandtzaeg P 
Published: January 2023

Abstract
Endothelial cells (EC) recruit circulating leukocytes to sites of inflammation, partly by expression of endothelial-leukocyte adhesion molecules. Whereas the regulation of some adhesion molecules is well characterized in cultured HUVEC, similar data for microvascular human test systems are limited. We studied the cytokine-regulated expression of vascular cell adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in cultured human intestinal microvascular endothelial cells (HIMEC). E-selectin and VCAM-1 were induced, and ICAM-1 was enhanced, in a dose-dependent fashion after stimulation with IL-1beta, TNF-alpha, and LPS. Each adhesion molecule displayed characteristic time-related responses comparable to those obtained with HUVEC, and each molecule supported adhesion of leukocytes. Notable disparities between the two endothelial test systems were that 1) expression of total cellular E-selectin (but not surface membrane expression) was sustained after 72 h of IL-1beta stimulation in HIMEC, contrasting a rapid biphasic response in HUVEC; 2) LPS did not maintain prolonged expression of ICAM-1 and VCAM-1 in HIMEC; and 3) VCAM-1 protein was dose-dependently up-regulated by IL-4 in HUVEC, peaking after 8 h, while IL-4 had only a negligible effect on the expression of this protein in HIMEC. In conclusion, the regulation of these adhesion molecules appears to be somewhat different in HIMEC compared with HUVEC, and the differences from available data on skin-derived microvascular endothelial cell cultures are to some extent substantial. Our findings document the importance of using relevant endothelial cell culture systems for studies of leukocyte-endothelial cell interactions.
Human eosinophils elaborate the lymphocyte chemoattractants. IL-16 (lymphocyte chemoattractant factor) and RANTES.
Authors: Lim K G , Wan H C , Bozza P T , Resnick M B , Wong D T , Cruikshank W W , Kornfeld H , Center D M , Weller P F 
Published: January 2023

Abstract
Eosinophils and CD4+ lymphocytes are preferentially recruited into sites of allergic inflammation. A role for eosinophils in the recruitment of CD4+ lymphocytes has not been defined. We studied the capacity of human eosinophils to release chemoattractants for T lymphocytes. Supernatants of cultured eosinophils contained chemoattractant activity for lymphocytes, which was predominantly due to IL-16 (lymphocyte chemoattractant factor) and RANTES. With neutralizing Abs, eosinophil-derived lymphocyte chemotactic activity was diminished by a mean (+/- SEM) of 60 +/- 3% with polygonal anti-IL-16 Ab, 69 +/- 4% with anti-IL-16 mAb, 48 +/- 3% with anti-CD4 F(ab) (IL-16 receptor blockade), 40 +/- 4% with anti-RANTES mAb, and 88 +/- 5% with a combination of anti-IL-16 and anti-RANTES mAbs. IL-16 and RANTES were detectable in eosinophil-derived supernatants by ELISA. Eosinophils constitutively expressed mRNA transcripts for both IL-16 and RANTES detectable by reverse transcription-PCR and contained preformed IL-16 and RANTES demonstrable by ELISA of cell lysates and by immunocytochemistry of freshly isolated eosinophils. Thus, eosinophils are a source of two cytokines, IL-16 and RANTES, that are chemoattractants for lymphocytes as well as eosinophils. These data indicate that eosinophils could contribute cytokines to enhance the recruitment of additional populations of CD4+ lymphocytes and eosinophils.
Ligation of the functional domain of complement receptor type 2 (CR2, CD21) is relevant for complex formation in T cell lines.
Authors: Prodinger W M , Larcher C , Schwendinger M , Dierich M P 
Published: January 2023

Abstract
We investigated the potential of CD21, the complement receptor type 2, to form receptor complexes with other membrane molecules on T cell lines. CD21 from T cell lines transformed with human T cell leukemia virus type I (MT2, HUT-102, C5.MJ, Mondi, and C91.PL) and T cell lines that were not virus transformed was analyzed by coprecipitation following cell lysis with digitonin. mAbs binding to functional and nonfunctional epitopes of CD21 and a polyclonal antiserum against its intracellular portion precipitated CD21, which was indistinguishable from CD21 on B cell lines. In contrast to B cells, where CD21 is complexed with CD19 and CD81 (target of anti-proliferative Ab 1) or, alternatively, with CD35 (CR1), no surface molecules could be coprecipitated with three of four mAbs from these T cell lines. Therefore, we assume that CD21 is not part of a preformed complex in T cell lines. OKB7, the only mAb directed against the functional C3d binding site, coprecipitated two proteins of 105 and 55 Mr with CD21 from MT2 and Mondi cells and from the T cell lines Jurkat E6-1 and SupT1. These bands were also recovered with CD21 precipitated from MT2 cells with C3d bound to Sepharose via the internal thioester, but were absent in CD21-expressing B cell lines. As C3d and OKB7 are functional ligands for B cells, we propose that upon ligation on T cells, CD21 associates with molecules of 105/55 Mr in the plasma membrane. Whether this is the first event of a signal delivered to the T cell is under current investigation.
The proteolytic environment involved in MHC class II-restricted antigen presentation can be modulated by the p41 form of invariant chain.
Authors: Fineschi B , Sakaguchi K , Appella E , Miller J 
Published: January 2023

Abstract
During biosynthesis, MHC class II associates with invariant chain which exists in two forms, p31 and p41. Both forms of invariant chain prevent peptide binding to class II, facilitate transport, and enhance class II localization to Ag-processing compartments. In spite of these shared functions, presentation of some Ags can be selectively enhanced by expression of p41. Here we show that p41 can function as a protease inhibitor: 1) the functional and biochemical consequences of p41 expression can be mimicked by inhibiting cysteine proteases in vivo; 2) the amount of intracellular active cysteine proteases is dramatically decreased in p41-positive cells; and 3) a polypeptide corresponding to the p41-unique region is a potent inhibitor of cathepsin L in vitro. These data suggest that p41 can enhance Ag presentation by reducing the proteolytic activity of the Ag-processing compartment, thus protecting a subset of antigenic epitopes from excessive degradation.
CD30 expression on human CD8+ T cells isolated from peripheral blood lymphocytes of normal donors.
Authors: Agrawal B , Reddish M , Longenecker B M 
Published: January 2023

Abstract
By direct or indirect immunofluorescence using FITC as a fluorochrome, 0 to 2% of the T cells isolated from peripheral blood of normal healthy individuals was found to be CD30+. Using indirect immunofluorescence and phycoerythrin-labeled Ab, higher percentages of CD30+ T cells (3-31%) were repeatedly found in the peripheral blood of normal healthy donors. The majority (85-90%) of CD30+ T cells obtained from PBLs of normal healthy donors were found in the CD8+ cell population. Following FACS sorting of the T cell populations into CD30+ and CD30- subpopulations, approximately 85 to 90% CD30+ T cells were CD8+, whereas the CD30- T cells were CD4+. Upon activation, the sorted CD30+ T cells produced both IFN-gamma and IL-4. In contrast to previous reports, these results demonstrate that CD30+CD8+ T cells are present in significant numbers in the PBLs of normal healthy individuals.
Infusion of anti-B7.1 (CD80) and anti-B7.2 (CD86) monoclonal antibodies inhibits murine graft-versus-host disease lethality in part via direct effects on CD4+ and CD8+ T cells.
Authors: Blazar B R , Sharpe A H , Taylor P A , Panoskaltsis-Mortari A , Gray G S , Korngold R , Vallera D A 
Published: January 2023

Abstract
Efficient T cell proliferation requires costimulation via CD28/B7 or other pathways. Graft-vs-host disease (GVHD) is caused by activated donor T cells. We have found that the infusion of anti-B7.1 (CD80) + anti-B7.2 (CD86) mAb is effective in eliminating GVHD lethality induced by either CD8+ or CD4+ T cells. Donor CD4+ and CD8+ T cell expansion was inhibited by almost 100-fold as measured by enumerating thoracic duct lymphocytes (TDL) obtained early post-transplant. TDL retained anti-host responsiveness indicating that not all T cells were anergic. Although anti-CD80 or anti-CD86 mAb individually were ineffective in preventing CD8+ T cell GVHD lethality, each mAb was partially effective in CD4+ T cell-mediated GVHD. Because CD80 expression was found to be up-regulated on donor CD4+ TDL post-transplant, the GVHD capacity of donor CD4+ T cells deficient in CD80 was tested and found to be reduced similarly to that seen with anti-CD80 mAb. These studies demonstrate that anti-CD80 + anti-CD86 mAb infusion is effective in preventing GVHD lethality by inhibiting donor CD4+ or CD8+ T cell expansion and provide the first evidence that CD80 expression on donor T cells is critical for optimal GVHD lethality.
Soluble protein but not peptide administration diverts the immune response of a clonal CD4+ T cell population to the T helper 2 cell pathway.
Authors: Degermann S , Pria E , Adorini L 
Published: January 2023

Abstract
BALB/c mice immunized with protein Ags such as OVA in adjuvant mount a Th1-type response. Inhibition of Th1 and development of Th2 cells can be induced by pretreating BALB/c mice with soluble OVA before priming. To investigate some aspects of this immune deviation in vivo, naive TCR transgenic T cells specific for the chicken OVA peptide 323-339 presented by I-A(d) molecules were adoptively transferred into normal BALB/c mice. The frequency and fate of the transferred T cells can be followed with an anti-clonotypic Ab. In response to priming with OVA in CFA, the transferred transgenic T cells expand and differentiate into Th1 cells producing IL-2 and IFN-gamma. If recipient mice are injected with soluble OVA before priming, the frequency of transgenic T cells is not affected, but their expansion in response to Ag priming is inhibited. Yet, the fewer transgenic T cells recovered are not anergic, they proliferate as control cells when restimulated in vitro by plate-bound anticlonotypic Ab or by Ag. Analysis of Th phenotype indicates that pretreatment with soluble OVA has suppressed Th1 cell differentiation in favor of the generation of Th2 cells producing IL-4 and IL-5. Pretreatment with soluble peptide 323-339 also inhibits Th1 cell development, but fails to induce Th2 cell differentiation. Thus, pretreatment with soluble protein Ag or with synthetic peptide inhibits Th1 cell development, but only protein, not peptide, administration can deviate the in vivo response of a clonal T cell population from the Th1 to the Th2 pathway.
Subcellular localization of CD80 receptors is dependent on an intact cytoplasmic tail and is required for CD28-dependent T cell costimulation.
Authors: Doty R T , Clark E A 
Published: January 2023

Abstract
CD28 provides a major costimulatory signal to T cells when it is cross-linked with mAb, immobilized recombinant ligand (CD80Ig or CD86Ig), or ligand-bearing cells but not when it is bound by specific Fab fragments or monomeric ligand. We wanted to determine how monomeric CD80 could cross-link CD28 since CD80 is expressed as a monomer on the surface of APC. We found that CD80 may interact with the actin-based cytoskeleton. To test whether the interaction of CD80 with the cytochalasin B-sensitive cytoskeleton was necessary for T cell costimulation through CD28, we constructed a tailless form of CD80 and generated stable transfectants of Chinese hamster ovary epithelial cells and Reh B cells expressing either the tailless or wild-type CD80 molecules. Unlike control cells expressing wild-type CD80, the tailless CD80 transfectants expressing equivalent levels of surface CD80 were not able to provide a costimulatory signal for anti-CD3-induced T cell proliferation, up-regulation of CD25 (IL-2Ralpha) expression, or the induction of IL-2 secretion. Thus, the cytoplasmic tail of CD80 apparently is required to signal T cells. Confocal microscopic studies revealed that wild-type CD80 and tailless CD80 have different patterns of subcellular distribution in both epithelial and lymphoid cells. Furthermore, T cell contact induces more patching and capping of CD80 in wild-type CD80-expressing cells than in tailless CD80-expressing cells. This suggests that the cytoplasmic region of CD80 functions to localize CD80 in complexes required for effective T cell costimulation.
IL-10 inhibits lipopolysaccharide-induced murine B cell proliferation and cross-linking of surface antigen receptors or ligation of CD40 restores the response.
Authors: Marcelletti J F 
Published: January 2023

Abstract
The effects of IL-10 on murine B cell proliferation in vitro were investigated. IL-10 inhibited LPS-induced B cell proliferation with an EC50 of approximately 500 pg/ml. IL-10-mediated inhibitory activity was not overtly associated with cytotoxicity or induction of apoptosis. The presence or the absence of T cells and mononuclear phagocytes did not affect the inhibitory activity of IL-10 on LPS-induced proliferation. LPS-stimulated, IL-10-exposed B cells progressed from G0 or from M to G1A of the cell cycle, but were inhibited from entry into subsequent phases. IL-10 had no discernible effect on B cell proliferation elicited with goat anti-mouse IgM plus IL-4. Moreover, cross-linking, but not mere ligation, of surface Ag receptors restored LPS-induced B cell proliferation in the presence of IL-10. The proliferative response to ligation of CD40 with anti-CD40 Abs was also not inhibited by IL-10, and as observed with goat anti-mouse IgM, the presence of such Abs in IL-10-containing B cell cultures allowed for the proliferative response to LPS. A variety of other Abs reactive with murine B cell surface markers were ineffective at modulating the response to IL-10. IL-1, IL-2, IL-4, IL-5, IL-6, IFN-gamma, and TGF-beta were also ineffective in this regard. These observations suggest that IL-10 has a role in the suppression of inappropriate B cell proliferation, i.e., proliferation by B cells that have not effectively interacted with relevant Ag or CD40 ligand.
p126 (CDw101), a costimulatory molecule preferentially expressed on mucosal T lymphocytes.
Authors: Russell G J , Parker C M , Sood A , Mizoguchi E , Ebert E C , Bhan A K , Brenner M B 
Published: January 2023

Abstract
Intestinal mucosal lymphocytes are defined by their anatomic location within the epithelium (intraepithelial lymphocytes), the interstitium between the epithelial basement membrane and the underlying muscularis mucosa (lamina propria lymphocytes), or in organized lymphoid tissues (Peyer's patches). Although intestinal intraepithelial lymphocytes have a distinct localization, their function has not been determined. To define cell surface proteins that are involved in intestinal intraepithelial lymphocyte localization or function, cultured human mucosal lymphocytes were used as immunogens to develop mAbs that react predominantly with this cell population in an immunohistochemical screening assay. Three mAbs were selected that subsequently were found by biochemical analysis to identify a 200-kDa homodimeric polypeptide on 88 to 98% of CD3+ mucosal lymphocytes but only 18 +/- 13% of PBLs. Expression on granulocytes and monocytes was also observed. This polypeptide has been termed p126 based on its SDS-PAGE-determined M(r) under reducing conditions. Cleveland digest maps demonstrated similarity between the p126 and CDw101 polypeptides. Determined amino acid sequence analysis of the purified p126 polypeptide revealed that it is the protein product of the recently identified V7 gene, which has structural similarities to members of the Ig gene superfamily. Two of the anti-p126 mAbs were costimulatory with suboptimal concentrations of anti-CD3 mAb inducing proliferation of cultured intestinal intraepithelial lymphocytes. Thus, we conclude that p126 is CDw101 encoded by a gene that predicts a seven-Ig domain chain-like structure. It has restricted expression predominantly on mucosal T lymphocytes and appears to have a costimulatory function of special relevance for CD28- T cells and for mucosal lymphocytes.
Herpes simplex virus blocks intracellular transport of HLA-G in placentally derived human cells.
Authors: Schust D J , Hill A B , Ploegh H L 
Published: January 2023

Abstract
Spontaneous fetal loss is associated with herpes simplex virus (HSV) infection as deduced from epidemiologic data. To date, the underlying mechanisms remain to be elucidated, but an immune component is suspected. HLA-G is a class I MHC molecule selectively expressed on extravillous cytotrophoblast; this cell type does not express conventional HLA-A or -B, whereas expression of novel HLA-C-like products has been reported. While its function remains unclear, a role for HLA-G in silencing NK cells that would otherwise attack cells devoid of classical class I molecules has been invoked. We here show that expression of HLA class I molecules is abrogated in HSV-infected choriocarcinoma cells, a phenomenon mediated by the virally encoded inhibitor of the transporter associated with Ag presentation, ICP47. These observations may provide a link between HSV infection and spontaneous fetal loss.
Changes in the cytoplasmic structure of CTLs during target cell recognition and killing.
Authors: Waters J B , Oldstone M B , Hahn K M 
Published: January 2023

Abstract
CTL play a critical role in immune defense by recognizing and killing virally infected or tumor cells. In this report, the structure of cytoplasm within living CTL was monitored during CTL killing of target cells. Living CTL were simultaneously loaded with fluorescent 70,000- and 10,000-kDa dextran particles. The relative distribution of the large and small dextrans within CTL revealed subcellular heterogeneities in the submicroscopic structure of cytoplasm. Localized alterations in cytoplasmic structure correlated with specific events during CTL killing. Recognition of target cells was accompanied by a transient increase in large dextran accessibility over a broad front near the interface between CTL and target cells. This region narrowed to a smaller area from which pseudopodia were extended toward the target. During extension, there was a large difference between regions of high dextran accessibility within the pseudopod and more structured cytoplasm within the cell body. Areas undergoing structural changes showed localized foci of high dextran accessibility. During retraction, cytoplasmic structure became gradually more uniform throughout the protrusion and cell body. These observations revealed subcellular regions undergoing major changes during early stages of the killing response, and addressed the role of cytoplasmic solation in controlling CTL morphology. They support mechanisms of pseudopod extension driven by hydrostatic pressure and demonstrate a precise regulation of cortical structure to control the direction of pseudopod extension.
Induction of apoptosis by anti-CD3 epsilon F(ab')2 in antigen receptor transgenic murine T cells activated by specific peptide.
Authors: Yu X Z , Zhu L , Davis J E , Tso J Y , Hansen J A , Anasetti C 
Published: January 2023

Abstract
Peripheral T cell tolerance can be achieved through deletion of mature CD4+ cells activated by high dose Ag. We tested whether apoptosis of peripheral CD4+ cells could be induced by a stimulatory dose of Ag plus a soluble ligand to the nonpolymorphic epsilon-chain of the TCR-associated CD3 complex. CD4+ T cells from the DO10 mouse express a transgenic TCR-alphabeta specific for OVA peptide 323-339 presented by I-A(d). OVA alone induced clonal activation and expansion of peripheral CD4+/TCR transgene+ cells. Simultaneous exposure to specific Ag plus soluble anti-CD3 Fos, a nonmitogenic anti-CD3epsilon genetically engineered F(ab')2-like Ab, blocked expansion and induced death of CD4+/TCR transgene+ cells, but not CD4+/TCR transgene- T cells. In contrast, a mitogenic anti-CD3epsilon Ab induced polyclonal activation and nonselective T cell death. Sequential stimulation by Ag followed by anti-CD3 Fos also induced death of TCR transgene+ cells, whereas stimulation by anti-CD3 Fos followed by Ag did not affect cell viability or function. Anti-CD3 Fos-induced death was associated with DNA fragmentation characteristic of apoptosis, was facilitated by IL-2, and was initiated by stimulation during the S-G2 phases of the cell cycle. Anti-CD3 Fos could induce deletion of Ag-activated T cells by apoptosis in vivo. Thus, a soluble, non-Fc-binding anti-CD3 Ab can induce programmed cell death of Ag-activated peripheral CD4+ T cells by CD3epsilon cross-linking during S or G2. Peripheral T cell deletion by activation-driven apoptosis is under cell cycle control and can be exploited to achieve selective immunosuppression by nonmitogenic anti-CD3epsilon Abs.
Analysis of a hot spot for DNA insertion suggests a mechanism for Ig switch recombination.
Authors: Baar J , Pennell N M , Shulman M J 
Published: January 2023

Abstract
We recently reported that transfected DNA inserts into the VDJ-Cmu intron much more frequently than into average DNA, and that insertion within this intron occurs preferentially into the switch region. To gain information about the mechanisms involved in DNA insertion, we sequenced the 5' and 3' junctions of typical transformants. Although the junction sequences did not indicate a preferred insertion motif within the switch region, our results suggest that joining of the transfected and chromosomal DNAs is facilitated by short regions of identity. Our analysis of the insertions into the non-switch part of the intron suggests that breakage of the chromosomal DNA occurs preferentially at sites that are flanked by short complementary sequences. This correlation suggests that the self-complementary DNA might form short stem-loops, which, in turn, are prone to enzymatic cleavage and thus facilitate the insertion of transfected DNA. A model is proposed in which this effect can account for both the higher than average frequency of insertion into the VDJ-Cmu intron and the preference for the switch region within this intron. An extension of this model is proposed to explain why the repetitive switch regions are the preferred breakage/rejoining sites for isotype switch rearrangements.