bluuebunny/crossref_metadata_2025_split huggingface dataset:
Appearance of granulocyte-macrophage colony-stimulating factor activity at allergen-challenged cutaneous late-phase reaction sites.
Authors: Massey W , Friedman B , Kato M , Cooper P , Kagey-Sobotka A , Lichtenstein L M , Schleimer R P 
Published: December 2022

Abstract
The cytokines IL-3 and granulocyte-macrophage CSF (GM-CSF) activate and/or prime monocytes, basophils, and eosinophils for a number of proinflammatory events in vitro. It was hypothesized that IL-3 and GM-CSF might also participate in the local inflammatory cascades that occur at cutaneous blister sites after Ag challenge in vivo. The M-07e megakaryocytic leukemia cell line, which proliferates in response to IL-3 or GM-CSF, was used to determine whether these cytokines were present in fluids derived after Ag challenge in the cutaneous blister chamber model. Fluids from blister chambers after either Ag (timothy grass, orchard grass, or ragweed) or vehicle control challenge were collected hourly for 12 h from nine patients with allergic rhinitis. Cytokine (IL-3/GM-CSF) activity was modestly elevated at 4 h after Ag challenge compared to control with the median of maximal proliferation 4% (range, 2 to 22%) vs 2% (range, 1 to 14%), respectively (Ag vs control, p &lt; 0.03). Activity peaked at 7 h (Ag = 10%, range 1 to 12%, vs control = 1%, range 1 to 9%, p &lt; 0.02) and then steadily declined. No increase in cytokine activity over control was seen in Ag-challenged nonatopics (n = 5, p = NS), indicating that release did not result from a nonspecific effect of the Ag solution. Neutralization of cytokine bioactivity in pooled late phase reaction (LPR) fluids from h 4 to 12 (n = 5) with anti-IL-3, anti-GM-CSF, or both antisera revealed that the majority of the activity was GM-CSF. To better quantify cytokine levels, pooled LPR fluids prepared from an additional 11 subjects were concentration-dialyzed (10x) and tested for cytokine activity. Pooled fluids from Ag-challenged sites contained a median of 625 pg/ml (range, 30 to 1250 pg/ml) GM-CSF equivalents, whereas those from the vehicle control-challenged sites contained a median 30 pg/ml (range, 30 to 300 pg/ml) GM-CSF equivalents (p &lt; 0.004 Ag vs control groups, n = 11). Concentrated fluid from Ag- and control-challenged sites in two nonatopic subjects contained &lt; 10 pg/ml cytokine activity. To evaluate the IL-3 and GM-CSF activity with a separate technique, ELISA were performed on separately pooled blister fluids from six atopic subjects. Although no IL-3 activity was detected after Ag challenge in these six subjects, all of them demonstrated levels of GM-CSF at Ag-challenged sites comparable to that found in the bioassay.(ABSTRACT TRUNCATED AT 400 WORDS)
Unmodified pancreatic islet allograft rejection results in the preferential expression of certain T cell activation transcripts.
Authors: O'Connell P J , Pacheco-Silva A , Nickerson P W , Muggia R A , Bastos M , Kelley V R , Strom T B 
Published: December 2022

Abstract
Polymerase chain reaction-assisted reverse transcription was used to study the temporal course of rejection in unmodified recipients of murine pancreatic islet cell allografts (DBA/2--&gt;B6AF1) by using syngeneic tissues as controls. The histologic appearance of the grafts was analyzed in parallel. Preproinsulin and constant region of the TCR-beta chain transcripts were studied as markers of graft integrity and infiltrating T cell mass, respectively. The participation of certain cytokines and CTL were analyzed by the detection of IL-2, IFN-gamma, IL-4, and CTL-specific serine protease (granzyme B) transcripts. The time-related disappearance of intragraft preproinsulin transcripts correlated with graft destruction, whereas the intensity of intragraft TCR-beta chain transcript levels correlated with the magnitude of mononuclear leukocyte infiltration in allografts. In unmodified allografts, the magnitude of IL-2 and IFN-gamma intragraft mRNA levels correlated with the intense mononuclear leukocyte infiltrate found on histologic examination at day 8. Only after stable IL-2 gene transcription on day 8 does evidence of graft destruction become apparent, indicating that IL-2 gene activation is closely related to and probably required for expression of alloimmune cytopathic processes. In contrast, IL-4 transcripts were absent or detected in low copy number throughout this time course. Intragraft expression of granzyme B mRNA, a CTL-specific transcript, peaked from day 8 to day 12 in allografts compared with syngeneic grafts or normal tissue. In syngeneic grafts IL-2 and/or IL-4 mRNA was essentially not detected. Although IFN-gamma and granzyme B transcripts were detected in syngeneic grafts, after 4 days the levels of detected transcripts were far less than those noted in allografts. In vivo detection of intragraft IL-2 transcripts in the relative absence of detectable IL-4 transcripts strongly suggests IL-2-dependent immune effector mechanisms are associated with, and perhaps responsible, for allograft rejection. Apparently IL-4-dependent effector mechanisms are not necessary for allograft rejection.
Control of lymphocyte recirculation in man. II. Differential regulation of the cutaneous lymphocyte-associated antigen, a tissue-selective homing receptor for skin-homing T cells.
Authors: Picker L J , Treer J R , Ferguson-Darnell B , Collins P A , Bergstresser P R , Terstappen L W 
Published: December 2022

Abstract
Recent work indicates that a novel homing receptor (HR)/endothelial ligand pair--the cutaneous lymphocyte-associated Ag (CLA) and E-selectin--is involved in targeting a unique skin-associated subpopulation of memory T cells to cutaneous sites of chronic inflammation. To investigate the regulatory mechanisms responsible for the generation of a memory T cell subset with skin-selective homing capability, we used multiparameter flow cytometry to assess the expression of CLA on T cells during initial T cell activation in secondary lymphoid tissues (the virgin to memory transition), and upon reactivation in skin. Our analyses indicate that in vivo induction of CLA (and E-selectin-binding ability) first occurs during the virgin to memory transition, and is regulated in a highly tissue-selective manner. The frequency of CLA expression on CD45RA+/RO+ transitional T cells within skin-associated peripheral lymph nodes was &gt; fivefold higher than within the mucosal microenvironment of the appendix. In keeping with its role as a skin-selective homing receptor, levels of cell-surface CLA on T cells obtained from cutaneous blisters overlying delayed-type hypersensitivity sites were a mean 23-fold higher than on corresponding peripheral blood T cells, including all time points of lesional evolution. However, comparisons of CLA expression on resting vs activated skin blister T cells (HLA-DR - vs +, respectively) indicated that CLA expression, which is already quite high on the resting subset, appeared to be further up-regulated upon activation in skin. The critical involvement of local microenvironments in the regulation of CLA expression was also supported by in vitro studies demonstrating the necessity of specific secondary signals for the induction of CLA glycoproteins on mitogen-activated T cells. CLA up-regulation on both the virgin and memory T cell subsets was dependent on the presence of TGF-beta 1 (or, to a lesser extent, IL-6), but not a wide variety of other cytokines. Thus, the development of the CLA+ memory T cell subset is likely a product of the cumulative experience of those T cells with respect to local microenvironments at previous sites of activation, perhaps involving differential availability of bioactive TGF-beta 1 and/or IL-6 (both cytokines produced in skin). Repeated activation in skin or skin-associated peripheral lymph nodes may act to reinforce CLA expression on T cells functionally-associated with skin, and thus enhance the functional efficiency of these cells by preferentially focusing their recirculation to the skin or related sites.
IFN-alpha induces homotypic adhesion and Leu-13 expression in human B lymphoid cells.
Authors: Evans S S , Collea R P , Leasure J A , Lee D B 
Published: December 2022

Abstract
IFN-alpha influences the recirculation and growth of normal and malignant B lymphocytes, although the mechanisms involved are not currently known. Lymphocyte recirculation is fundamentally dependent on cell-to-cell interactions that are mediated by cell surface adhesion molecules. In this report, we examined the relationship between the effect of IFN-alpha on cell-to-cell adhesion processes and induction of the Leu-13 cell surface protein in established human Daudi B lymphoid cell lines that are either sensitive or resistant to the antiproliferative activity of IFN-alpha. IFN-alpha directly triggered homotypic adhesion of IFN-sensitive Daudi B cells in a time- and dose-dependent manner. In contrast, IFN-alpha had no effect on the cell-to-cell adhesion of IFN-resistant Daudi B cells. The capacity of IFN-alpha to trigger homotypic aggregation correlated directly with the level of induction of the cell surface protein Leu-13 and could be potentiated by anti-Leu-13 mAb. Other cytokines also known to influence the proliferation, differentiation, or recirculation of B lymphocytes such as IFN-gamma, IL-2, IL-4, IL-6, TNF-alpha, and low molecular weight B cell growth factor did not induce either Leu-13 expression or homotypic aggregation of Daudi B cells. The adhesion pathway triggered by the IFN-inducible protein Leu-13 required metabolic energy and an intact cytoskeleton but was not dependent on: 1) new protein synthesis; 2) protein kinase C, protein kinase A, or tyrosine kinase activities; or 3) the function of known adhesion molecules including LFA-1, ICAM-1, CD44, or VLA-4. Taken together, these studies demonstrate a fundamental role for IFN-alpha and the IFN-inducible protein Leu-13 in regulating a novel homotypic adhesion pathway in B lymphocytes, and provide insight into the possible mechanisms by which IFN-alpha regulates biologic processes including recirculation.
Activity of stem cell factor and IL-7 in combination on normal bone marrow B lineage cells.
Authors: Funk P E , Varas A , Witte P L 
Published: December 2022

Abstract
The production of B cells is regulated by soluble and cell contact signals presumably provided by bone marrow stromal cells. Among these is IL-7, a well characterized proliferative stimulus for a subset of pre-B cells. Stem cell factor (SCF), a stromal cell-derived cytokine with broad hemopoietic effects, has been reported to synergize with IL-7 to drive the proliferation and differentiation of B220- bone marrow cells into B220+ B cell precursors in long term culture. A subsequent report has cast doubt on this result by showing that SCF and IL-7 were incapable of producing mu+ pre-B cells after short term culture. Here, using the cell sorter to assure discrete separation of B220+ and B220- cells followed by soft agar culture to prevent interaction with accessory cells, we demonstrate that the combination of SCF and IL-7 does not stimulate the expansion or differentiation of B220- lymphoid precursors but can act synergistically in the clonal proliferation of B220+ cells.
Influence of protein-quaternary structure on antigen processing.
Authors: Rouas N , Christophe S , Housseau F , Bellet D , Guillet J G , Bidart J M 
Published: December 2022

Abstract
T cell recognition of the quaternary structure of human chorionic gonadotropin (hCG), resulting from the association between its alpha (hCG-alpha) and beta (hCG-beta) subunits, was analyzed using hCG-alpha and hCG-beta T cell hybridomas produced in BALB/c mice. First, the fine specificity of these T cell hybridomas was determined, enabling us to divide hCG-alpha-specific T cell hybridomas into two groups. Group I recognized the hCG-alpha(61-81) region, and group II responded to the hCG-alpha(50-70) part of the molecule. Two groups of hCG-beta-specific T cell hybridomas, designated groups III and IV, were analyzed and found to respond to the C- and the N-terminal parts of the hCG-beta(1-22) peptide, respectively. Moreover, we observed that the nature of APC influenced Ag recognition by hCG-beta T cell hybridomas from group IV, but not by other selected T cell hybridomas. We then showed that recognition of the hCG alpha/beta dimer by alpha-specific T cell hybridomas was dramatically reduced compared to both free hCG-alpha and heat-dissociated hCG alpha/beta molecules. In contrast, hCG-beta hybridomas exhibited comparable responses to the free beta subunit and the hCG dimer. Experiments using a dimeric molecule assembled from the alpha-subunit of human follicle-stimulating hormone, which is identical to hCG-alpha, and the beta-subunit of human follicle-stimulating hormone, which is homologous to hCG-beta, confirmed that the three-dimensional structure of the complex rather than the primary structure of the beta-subunit plays a critical role in the processing pathway. Finally, kinetic experiments showed that the presentation of hCG-alpha T cell epitopes differed depending upon whether the alpha-subunit was in its free or combined form. In contrast, the kinetic expression of hCG-beta T cell epitopes appeared to be independent of the quaternary structure of hCG. Thus, conformational alterations resulting from the alpha/beta subunit association mainly influenced processing of the alpha-subunit in its complexed form, rather than processing of the combined beta-subunit. The effect of protein-quaternary structure on T cell recognition may represent a new element in our understanding of the processing and presentation of oligomeric molecules.
Molecular structure of a cross-reactive idiotype on autoantibodies recognizing parenchymal self.
Authors: Karp S L , Kieber-Emmons T , Sun M J , Wolf G , Neilson E G 
Published: December 2022

Abstract
The autoimmune B cell repertoire in anti-tubular basement membrane (alpha TBM) disease is focused on the nephritogenic P1 domain of the 3M-1 target Ag in kidney and normally expresses a disease-modifying cross-reactive Id (IdX). The molecular structure of this Id was determined from a library of rat mAb alpha TBM/alpha 3M-1 by using anchor polymerase chain reactions. Our findings provide the first alignment of V region sequences for rat IgG and reveal that specificity for the P1 domain among alpha 3M-1 antibodies is derived from several recurring germ-line VH genes which have not undergone somatic mutation. The IdX in this repertoire localizes to the H chain on Western blot, and to the CDR3 region as deduced from the cDNA encoding several informative clones. Computer modeling of the Id reveals a conformational structure largely dependent on hydroxyl groups in or near turn position 4 of the H chain CDR3 region. These findings demonstrate that regulatory elements protective of autoimmunity are not encoded in the germ line as IdX, but rather emerge from a recombinatorial diversity engaged by the recognition of parenchymal self.
CD4+ subset expression in murine candidiasis. Th responses correlate directly with genetically determined susceptibility or vaccine-induced resistance.
Authors: Romani L , Mencacci A , Cenci E , Spaccapelo R , Mosci P , Puccetti P , Bistoni F 
Published: December 2022

Abstract
Previous work has shown that in hybrid (BALB/cCr x DBA/2Cr)F1 mice the development of a fatal disseminated disease by systemic infection with virulent Candida albicans is associated with the detection of strong Th2-like responses. However, a predominant Th1-like response and long-lived antifungal protection are induced by vaccinating these mice with live blastospores of attenuated C. albicans strains. When injected into DBA/2Cr mice, one such live vaccine strain was found in the present study to result in a progressive disease characterized by strong Th2 responses. Elevated serum IgG1, IgA, and IgE responses, weak or absent footpad reactions, sustained production in vitro of Th2 (IL-4 and IL-10) but not Th1 (IL-2 and IFN-gamma) cytokines by CD4+ cells, and eosinophilia were all detected in DBA/2 mice after infection with the attenuated vaccine. This was in marked contrast with the development of strong Th1 responses and persistent anticandidal protection in similarly infected, H-2-compatible BALB/cCr mice. Therefore, our data suggest that the type of Th response that predominates in mice after C. albicans infection correlates with genetically determined susceptibility or vaccine-induced resistance. Moreover, the genetic control of this resistance may not be associated with the H-2 complex.
CD28- T lymphocytes. Antigenic and functional properties.
Authors: Azuma M , Phillips J H , Lanier L L 
Published: December 2022

Abstract
A subset of CD8+ alpha beta-TCR/CD3+ T lymphocytes in adult human peripheral blood lacks expression of CD28, a membrane receptor for the B7/BB1 B cell differentiation Ag that is involved in T cell activation. CD28-8+ T cells were not observed in the thymus and were present at only low frequency in cord blood, suggesting that these cells may represent a type of "memory" population. Consistent with this interpretation, CD28-8+ T cells were morphologically large, granular lymphocytes and expressed CD54 (intercellular adhesion molecule-1), CD58 (lymphocyte function-associated Ag-3 (LFA)), and high levels of CD11a (LFA-1), but did not express Ag associated with acute activation (e.g., HLA-DR, CD25, CD69). Freshly isolated CD28-8+ T lymphocytes mediated potent anti-CD3 redirected cytotoxicity against FcR-bearing targets, demonstrating that the CD3/TCR complex is functional and that these cells possess cytolytic activity. However, the anti-CD3-induced proliferative response of CD28-8+ T cells was substantially less than CD28+8+ T cells and this deficiency could not be overcome by addition of exogenous IL-2. A large panel of T cell clones were produced from the CD28+8+ and CD28-8+ T cell populations by single cell sorting using a flow cytometer. CD28 expression was stable on clones derived from CD28+8+ T lymphocytes, whereas CD28 expression was quite variable and apparently reexpressed on some clones generated from the CD28-8+ T cell population. As with the freshly isolated cells, CD28-8+ T cell clones were cytotoxic, but anergic to anti-CD3- induced proliferation and could not be costimulated using B7 or CD58 (LFA-3) murine L cell transfectants. These results indicate that CD28- and CD28+ T cells may play different roles in an immune response.
Antigen-independent processes in antigen-specific immunity. A role for alpha 4 integrin.
Authors: Ferguson T A , Kupper T S 
Published: December 2022

Abstract
It has been proposed that the migration of immune T cells out of blood vessels through connective tissue to the site of antigenic challenge is facilitated by the interaction of VLA integrins on lymphocytes with endothelial cell adhesion molecules and matrix proteins. Indeed, we have recently demonstrated that peptides derived from sequences in fibronectin abrogate the T cell-mediated contact hypersensitivity (CHS) reactions in vivo. These peptides blocked the interaction of the integrins VLA-4 and VLA-5 with fibronectin (FN), and our results suggested that by preventing the interaction of T cell integrins with FN, we successfully prevented the migration of T cells to sites of antigenic challenge. To further explore the role of integrins in T cell migration, we have used an antibody (R1-2) specific for the alpha-chain of alpha 4 integrins. Our data show that this antibody stains more than 90% of CD3+ T cells, and this percentage does not change after the mice have been immunized with a contact sensitizer. We also show that this antibody blocks the interaction of cells with immobilized FN and vascular cell adhesion molecule-1 on activated endothelial cells. Although R1-2 identifies alpha 4 integrin on a large number of T cells, it does not discriminate between activated and resting forms of this integrin, because very few T cells from immune or nonimmune mice actually bind FN or activated endothelium. In vivo, antibody R1-2 effectively blocks Ag-specific CHS, but has little effect on the non-Ag-specific cells that localize to the site of antigenic challenge. The population of cells that adoptively transfer CHS exits with the population of cells that bind to FN or to activated endothelial cells. Our data demonstrate that a small number of Ag-specific T cells use alpha 4 integrin to enter sites of inflammation and mediate effector immune responses. Ag-independent accumulation of T cells near sites of inflammation does not appear to be mediated by alpha 4 integrin.
An evaluation of mechanisms by which tolerance to organ-specific antigens is lost using a transgenic mouse model.
Authors: Martin L , Mora-Worms M , Lucas C , Reynolds C , Stewart T A 
Published: December 2022

Abstract
Patients with type I diabetes lose immunologic tolerance to beta cell Ag and produce anti-self (beta cell) antibodies. We have examined mechanisms by which this self tolerance is lost using transgenic mice in which islet cells express human CD4. These mice are immunologically tolerant to this human protein; the tolerance appears to be characterized by the presence of self reactive B cells and nonresponsive T cells. Autoantibodies can be induced by immunization with CD4 in CFA; this autoantibody response is accompanied by minor peri-islet inflammation but diabetes is not induced. Tolerance can also be broken by provision of an independent covalently linked T cell epitope. Although this mimic can lead to the appearance of an autoantibody response, the autoimmune response can not be maintained by the endogenous Ag. We have also demonstrated that an inflammatory lesion leading to death of the CD4-containing beta cells may not be sufficient to break tolerance. These results have implications for potential mechanisms relating to the appearance of autoantibodies in patients with type I diabetes.
Inhibition of tyrosine phosphorylation prevents IFN-gamma-induced HLA-DR molecule expression.
Authors: Ryu K , Koide Y , Yamashita Y , Yoshida T O 
Published: December 2022

Abstract
We have previously demonstrated that HLA-DR molecule expression induced by IFN-gamma is associated with phosphatidylinositide turnover, activation of protein kinase C, and elevation of intracellular calcium. Because phosphorylation of phospholipase C-gamma 1 on tyrosine residues is known to be involved in the activation of phosphatidylinositide turnover, we investigated the role of tyrosine protein kinase (TPK) in the signal transduction for IFN-gamma-inducible DR molecule expression on T98G cells. The effects of three specific TPK inhibitors, genistein, herbimycin A, and tyrphostin, suggest that TPK is involved in the signal transduction. These inhibitors inhibited the IFN-gamma-inducible DR molecule expression in a dose-dependent manner. Being consistent with this, immunoblotting with an anti-phosphotyrosine mAb revealed that IFN-gamma induces a rapid increase in protein tyrosine phosphorylation. Genistein not only abrogated the IFN-gamma-induced enhancement of tyrosine phosphorylation, but also inhibited the IFN-gamma-induced production of inositol-4-5-triphosphate and the elevation of intracellular calcium. However, these three TPK inhibitors failed to inhibit the DR molecule expression induced by PMA and A23187. These findings suggest that the tyrosine phosphorylation is an early and critical event that precedes phosphatidylinositide turnover leading to activation of protein kinase C and elevation of intracellular calcium concentration during IFN-gamma-inducible DR molecule expression.