bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogenic MHC class II determinant(s) in MRL/Ipr autoimmune disease-prone mice. Unusual expression of an L1 transposable element creates molecular mimicry.
Authors: Bobé P , Benihoud K , Kiger N 
Published: December 2022

Abstract
In some aged MRL/Ipr autoimmune disease-prone mice, unexpected reactivity has been observed between lymphoid cells and mAb or polyclonal antibodies directed against the A beta d class II chain of the MHC. However, Southern blot analysis of their genomic DNA, using different class I and class II MHC-specific probes, confirmed their inbred character and their H-2k genotype. In this study, immunoprecipitation experiments with an anti-A beta d mAb indicated that the 45 (and 12)-kD molecule(s) recognized by an anti-A beta d mAb differed from a class II chain. After specific antibody screening of a lambda gt11 expression library constructed with MRL/Ipr "A beta d-positive" lymphoid cells, we cloned cDNA that share sequences with high homology (&gt; 80%) to the 3' end of a 7-kb L1Md (L1) element propagated in the mouse genome via retrotransposition. Northern blot analysis showed an overtranscription of these L1 sequences in the MRL/Ipr spleen cells used for the construction of the cDNA library, in comparison to the MRL ancestor strains. Therefore, the autoimmune MRL/Ipr strain could express a translation product of L1 open reading frame 2, which mimics a "highly antigenic" epitope of an allogenic MHC class II Ag.
Parameters of tolerance induction by antigen targeted to B lymphocytes.
Authors: Eynon E E , Parker D C 
Published: December 2022

Abstract
We have shown that a foreign protein Ag (the F(ab) fragment of rabbit IgG) becomes a particularly effective tolerogen when it is targeted to B lymphocytes in vivo. This is done by injecting the Ag intravenously into mice in the form of the F(ab) fragment of rabbit anti-mouse IgD antibody (F(ab)) rabbit anti-delta). Our hypothesis is that resting B cells are tolerogenic APC for CD4+ T cells in unprimed animals, and induce Ag-specific nonresponsiveness in the Th cell compartment by presenting Ag without appropriate costimulatory signals. In this report, we find that Ag-activated T cells appear to be resistant to tolerance induction, because F(ab) rabbit anti-delta given 5 days after challenge with rabbit F(ab) in alum adjuvant has little or no effect of the subsequent antibody response. Tolerance also fails in this model when B cells are activated independently of Ag by simultaneous injection of activating concentrations of divalent, IgG mouse anti-delta at the same time as F(ab) rabbit anti-delta. Finally, nonresponsiveness in the T cell compartment is not limited to a lesion in T cell help for the antibody response, because T cells from mice treated with F(ab) rabbit anti-delta and then primed with rabbit F(ab) fragments in CFA show reduced T cell proliferation and IL-2 production when restimulated with Ag in vitro.
A B lymphocyte surface molecule mediating activation and protection from apoptosis via calcium channels.
Authors: Santos-Argumedo L , Teixeira C , Preece G , Kirkham P A , Parkhouse R M 
Published: December 2022

Abstract
A rat mAb (NIM-R5) was prepared against a 42-kD B cell activation Ag (p42). The expression of p42 is increased upon activation. NIM-R5 induces an increase of intracellular Ca2+, due to influx from the exterior milieu via calcium channels. This stimulation does not prejudice further stimulation with anti-Ig, and thus p42 constitutes an activation signal independent of membrane Ig. The antibody induces increased expression of class II molecules on resting B lymphocytes and prepares the cells for "spreading" when interacted with immobilized anti-class II antibody. The antibody alone is weakly mitogenic and comitogenic with IL-4 on resting B cells. Of particular interest, NIM-R5 induces proliferation and rescue from apoptosis in B cells activated in vitro. In conclusion, NIM-R5 induces an Ig-independent activation and proliferation of resting and activated B cells. This antibody does not recognize other known B cell activation Ag such as CD23, CD40, or CD72. We therefore propose that the p42 Ag is a glycoprotein with an important role in the regulation of B lymphocyte activation and survival.
Granulocyte-macrophage colony-stimulating factor, but not macrophage colony-stimulating factor, suppresses basal and lipopolysaccharide-stimulated complement factor production in human monocytes.
Authors: Høgåsen A K , Hestdal K , Abrahamsen T G 
Published: December 2022

Abstract
Monocyte/macrophage contribution of C biosynthesis is important, particularly during inflammation. Since granulocyte-macrophage CSF (GM-CSF) and macrophage-CSF (M-CSF) exert a variety of stimulatory effects on monocyte/macrophage functions in vitro, we studied their impact on the biosynthesis of the C components C3 and factor B by human monocytes in culture. GM-CSF at doses of 10 ng/ml and higher inhibited the basal C3 synthesis. This effect was most pronounced when the cytokine was added to freshly isolated monocytes. No effect was found on the basal production of factor B. Furthermore, GM-CSF abrogated the LPS-stimulated production of both C3 and factor B. These suppressive effects were neutralized by a polyclonal anti-GM-CSF antibody. Moreover, when anti-GM-CSF was added to unstimulated or LPS-stimulated cells, their C3 production increased. This indicates that both spontaneous and LPS-triggered release of monocyte-produced GM-CSF has an autocrine function in regulating monocyte C3 biosynthesis. GM-CSF also down-modulated the expression of CD14 at an early stage of cell culture. This might be the mechanism through which the LPS-effects are suppressed because CD14 has been shown to be a LPS receptor. Contrary to this, M-CSF at doses of 100 U/ml and higher stimulated the synthesis of C3, whereas the basal production of factor B and the LPS-stimulated production of C3 and factor B were unaffected. Granulocyte-CSF (G-CSF) did not influence monocyte C biosynthesis, and neither anti-M-CSF nor anti-G-CSF influenced the LPS-induced C3 production. The effects of GM-CSF and M-CSF on C biosynthesis may be important in regulating the availability of C components during an inflammatory response, and these observations may also have implications for the clinical use of CSF.
Human mast cells produce IL-8.
Authors: Möller A , Lippert U , Lessmann D , Kolde G , Hamann K , Welker P , Schadendorf D , Rosenbach T , Luger T , Czarnetzki B M 
Published: December 2022

Abstract
Recruitment of neutrophils is a common feature in diseases that are associated with mast cell activation. The mechanisms that mediate neutrophil activation are not well understood. IL-8 is a recently described potent chemotactic factor that might be pathogenetically involved in this process. We therefore studied the human mast cell line HMCI and human skin mast cells for their ability to produce IL-8 using various stimuli. IL-8-mRNA was expressed in a stimulus- and time-dependent fashion as detected by Northern blot analysis with an IL-8-specific cDNA probe. The molecular mass of HMCI-derived IL-8 was determined to be about 8 kDa by immunoblot analysis. Immunoreactive and biologically active IL-8 protein was measured in the cell culture supernatants of HMCI cells by an ELISA and a chemotaxis assay, respectively. On immunoelectron microscopy of stimulated skin mast cells, IL-8 was found along cytoplasmatic membranes and in intracellular granules. Our data indicate that mast cells may contribute to neutrophil recruitment by secretion of IL-8.
Retina and retinal pigment epithelial cell autoantibodies are produced during murine coronavirus retinopathy.
Authors: Hooks J J , Percopo C , Wang Y , Detrick B 
Published: December 2022

Abstract
The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase of the disease, day 1 to 7, a retinal vasculitis is noted and is associated with the presence of virus particles. In the late phase of the disease, day 10 to 140, a retinal degeneration is observed and is associated with the absence of both virus particles and inflammatory cells. We show that the retinal degenerative process is also associated with the presence of antiretinal autoantibodies. In total, 22 of 23 sera collected from 10 to 70 days after JHM virus inoculation contained antiretinal autoantibodies. These autoantibodies are not found in sera from normal or mock-injected mice. Antibodies to retinal tissue were identified as two distinct patterns of immunoperoxidase staining on frozen sections of normal rat eyes, retinal autoantibodies and retinal pigment epithelium (RPE) autoantibodies. The antiretinal autoantibodies first appeared as IgM class antibodies that shifted to IgG class autoantibodies. The anti-RPE cell autoantibodies were predominantly of the IgG class. Sera that were positive for these autoantibodies did not stain with liver or kidney sections but 2 of 3 did react with rat brain sections. A second mouse strain, CD-1, was also evaluated because these animals respond to JHM virus inoculation by developing only the early phase of this disease, i.e. vasculitis. On day 10 postinoculation, the retina architecture has a normal appearance. In these mice, which are free of a retinal degeneration, antiretinal autoantibodies are not produced. However, just as is noted in the BALB/c mice, antivirus neutralizing antibodies are produced in the infected CD-1 mice. These findings suggest a role for autoimmunity in the pathogenesis of murine coronavirus induced retinal degeneration. This study establishes an animal model for the study of humoral autoimmune responses in human retinal degenerations.
Intracellular transport of class I MHC molecules in antigen processing mutant cell lines.
Authors: Anderson K S , Alexander J , Wei M , Cresswell P 
Published: December 2022

Abstract
Intracellular transport and stability of class I MHC glycoproteins depends on the assembly of H chain, beta 2-microglobulin, and peptide. The Ag processing mutant cell lines T2 and RMA-S have defects in peptide loading of class I, resulting in reduced cell surface expression of class I molecules. Expression of class I molecules in the murine cell line RMA-S can be induced at 26 degrees C, suggesting that they are transported to the cell surface, but are unstable. However, most human class I molecules in T2 are poorly expressed at the cell surface, even at 26 degrees C. To directly compare the transport of human and mouse alleles in RMA-S and T2, the human alleles HLA-A2, A3, and B27 were transfected into RMA-S along with human beta 2-microglobulin, and the mouse alleles H-2Kb and Db were transfected into T2. Surface expression of HLA-A3 and B27 in RMA-S remained less than 10% of wild-type levels at 26 degrees C. H-2Kb and Db in both cell lines, however, were expressed at 20 to 30% wild-type levels at 37 degrees C and could be induced to wild-type levels at 26 degrees C or with peptides. The selective expression of murine class I glycoproteins at the cell surface of T2 is not because of their greater stability when associated with human beta 2m, since H-2Kb and Db H chain/human beta 2m complexes dissociate more rapidly in vitro than HLA-A3 and B27 complexes. These results suggest that the difference in transport between human and mouse class I in T2 reflects a fundamental structural property of the class I glycoproteins.
Selection of the T cell receptor repertoire in Lpr mice.
Authors: Herron L R , Eisenberg R A , Roper E , Kakkanaiah V N , Cohen P L , Kotzin B L 
Published: December 2022

Abstract
The development of double-negative (CD4-, CD8-) T cells and other T cells subsets in lymphoproliferation (lpr) mice continues to be poorly defined. Recent studies indicate that lpr is a mutation of a receptor mediating apoptosis. It has thus been hypothesized that T cell development in the thymus should be abnormally affected. In this study, we analyzed the TCR V beta repertoire of double-negative T cells as well as CD4+ and CD8+ single-positive subsets in various lpr and matched non-lpr strains. Particular comparisons were made to determine the influence of different class I and class II molecules on repertoire formation. The data demonstrate that positive and negative selection of the CD4+ and CD8+ subsets are normal in lpr mice when compared with non-lpr congenic mice. Surprisingly, the result also suggest that double-negative T cells are mostly selected on class I MHC molecules in a pattern similar to the CD8+ population, and that T cells positively selected on class II MHC antigens may be absent from the double-negative population. In all lpr strains, we also found an increased percentage of double-negative V beta 8.3+ cells out of proportion to levels in the CD4+ or CD8+ subsets. Longitudinal studies and studies in thymectomized animals showed that this increase reflects a peripheral process selectively affecting V beta 8.3+ double-negative T cells. Together, these repertoire data provide new insight into the effect of the lpr genetic defect on T cell development and the derivation of double-negative T cells. Despite the role of Fas in apoptosis and the abnormal expression of this gene in lpr mice, the present results support the hypothesis that thymic events are relatively normal in lpr mice, and that the double-negative T cells are mostly class I MHC selected and expanded by abnormal peripheral processes.
Processing of endogenously synthesized hen egg-white lysozyme retained in the endoplasmic reticulum or in secretory form gives rise to a similar but not identical set of epitopes recognized by class II-restricted T cells.
Authors: Adorini L , Guéry J C , Fuchs S , Ortiz-Navarrete V , Hämmerling G J , Momburg F 
Published: December 2022

Abstract
To study the processing and presentation of endogenously synthesized Ag to class II MHC-restricted T cells, hen egg lysozyme (HEL), either tagged with a peptide that confers retention in the endoplasmic reticulum (HEL.KDEL), or in the secretory form (HELs), was stably expressed in LK-35.2 B hybridoma cells. Presentation of HEL peptides bound to class II molecules was assessed by activation of specific T cell hybridomas recognizing seven different epitopes derived from exogenous HEL. The presentation of endogenously synthesized HEL was not caused by reuptake of secreted of shed Ag. All the HEL epitopes examined were efficiently presented after processing of endogenous HEL by HELs-transfected LK-35.2 cells. Processing of HEL tagged with KDEL, however, gave rise to presentation of only six of the seven HEL epitopes. The epitope included in the HEL sequence 112-124 was not presented by HEL.KDEL-transfected B cells. In addition, two of the four T cell hybridomas recognizing HEL 116-129 together with I-Ak molecules were not activated by HEL.KDEL, and three other epitopes were presented with lower efficiency as compared with HELs. Thus, endogenously synthesized HEL in secretory form gives rise to a set of class II-binding epitopes indistinguishable from exogenous HEL, whereas endoplasmic reticulum-retained HEL generates a similar but not identical set of epitopes. The endosomal protease inhibitor leupeptin prevented presentation of the epitope 108-116, but not 46-61, both by HELs and HEL.KDEL transfected cells, indicating a requirement for endosomal processing in both cases. In addition, the presentation of peptides derived from endogenously synthesized, either secretory or endoplasmic reticulum-retained HEL, could be inhibited by lysosomotropic amines, further indicating that the intracellular route of class II molecules presenting peptides derived from endogenous Ag intersects the acidic endosomal compartment.
Endogenous IL-1 receptor antagonist protein (IRAP) regulates schistosome egg granuloma formation and the regional lymphoid response.
Authors: Chensue S W , Bienkowski M , Eessalu T E , Warmington K S , Hershey S D , Lukacs N W , Kunkel S L 
Published: December 2022

Abstract
This study examined the role of IL-1 receptor antagonist protein (IRAP) in the regulation of the immune/inflammatory response to schistosome eggs. Initial screening for IRAP-specific mRNA transcripts by reverse transcriptase and primer-directed polymerase chain reactions suggested significant endogenous IRAP synthesis in lungs with Schistosoma mansoni egg-induced hypersensitivity granulomas but not in normal lungs or lungs with non-immune bead granulomas. Direct detection using mIRAP-specific antibodies corroborated the RNA studies. Both ELISA and immunohistochemical studies revealed significant spontaneous IRAP production in cultures of isolated egg granulomas and regional reactive lymphoid tissue that could be localized largely but not exclusively to macrophages. Synchronously developing secondary schistosome egg granulomas showed accelerated and augmented IRAP production compared with primary lesions, paralleling granuloma cellularity and growth kinetics. Nonimmune T cell-independent bead lesions produced the least amounts of IRAP. In draining lymphoid tissue the onset of IRAP production corresponded with local cell proliferation in both primary and secondary egg responses. Next, the in vivo role of IRAP was tested by administration of anti-IRAP antisera which caused 40-50% increases in egg granuloma area. Moreover, treatment increased (50-100%) IL-2, IL-4, IL-10, and IFN-gamma production in the primary response and all but IFN in secondary response lymph node cultures. Our results suggest that IRAP is an endogenous regulatory protein and may limit the activity of IL-1 during the Ag-specific granulomatous response to schistosome eggs. Furthermore, our findings provide in vivo support for the notion that Ag-elicited lymphocyte-derived products probably augment IRAP production and block the action of IL-1.
Identification of human melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes.
Authors: Storkus W J , Zeh H J , Maeurer M J , Salter R D , Lotze M T 
Published: December 2022

Abstract
Using a newly described pH 3.3 acid elution technique, peptides were extracted by denaturation of class I molecules on the surface of human melanomas. HPLC fractionation of this material revealed six T cell epitopes (termed P1-P6) recognized by HLA-A2-restricted, melanoma-specific tumor infiltrating lymphocyte (TIL) lines. Three of these fractions (P1, P2, and P4) appeared to represent shared/immunodominant melanoma Ag recognized in the context of HLA-A2 because they were expressed by 4/4 HLA-A2+ melanoma cell lines and were each recognized by all four oligoclonal HLA-A2-restricted TIL lines examined. Interestingly, P1 and P2 (but not P3-P6) could also be recognized by these same TIL when presented by the HLA-Aw69 class I molecule, which is closely related to HLA-A2. P3, P5, and P6 displayed more restricted expression and were differentially recognized by the four oligoclonal TIL lines. These results suggest that synthetic peptide derived from P1, P2, and P4 sequences (when deduced) may form the basis of effective prophylactic or therapeutic melanoma vaccines by stimulating CD8+ CTL in HLA-A2+ individuals. This approach of identifying T cell epitopes presented by class I molecules should prove generally applicable to the study of other tumors recognized by class I-restricted CTL.
Lipopolysaccharide-induced protein tyrosine phosphorylation in human macrophages is mediated by CD14.
Authors: Weinstein S L , June C H , DeFranco A L 
Published: December 2022

Abstract
Induced protein tyrosine phosphorylation is an early intracellular event in LPS-stimulated murine macrophages that appears to play a role in signal transduction. We have now demonstrated that LPS also increases protein tyrosine phosphorylation in human monocyte-derived macrophages and in the human monocytic cell line, THP-1. This response was rapidly elicited by biologically active forms of LPS or lipid A, at concentrations of these bacterial components that stimulate anti-bacterial responses by human macrophages. Inhibition of the LPS-induced tyrosine phosphorylation response with the tyrosine kinase inhibitor, herbimycin A, was accompanied by the inhibition of the secretion of TNF-alpha by human macrophages. These results extend previous work with murine macrophages and provide further support for the hypothesis that induced protein tyrosine phosphorylation is an important signaling reaction in macrophages after LPS exposure. In addition, CD14, which is thought to be a receptor for LPS, appeared to mediate the induced phosphorylation response in human macrophages and THP-1 cells at low LPS concentrations. Two antibodies against CD14, 3C10 and 60b, which have been shown to prevent LPS binding to CD14, specifically inhibited the protein tyrosine phosphorylation induced by nanogram per milliliter concentrations of LPS in these cells. The antibody-mediated inhibition did not appear to involve engagement of surface FcR because a preparation of F(ab')2/Fab fragments of the 60b antibody also prevented LPS-induced tyrosine phosphorylation. At higher concentrations of LPS (&gt; or = 10 ng/ml), however, anti-CD14 antibodies did not prevent the induction of protein tyrosine phosphorylation, suggesting that a lower affinity CD14-independent pathway also mediates the tyrosine phosphorylation response. Because CD14-dependent and CD14-independent recognition of LPS appear to lead to the same functional responses by macrophages, induced protein tyrosine phosphorylation may be part of a shared intracellular signaling pathway.
Co-stimulatory signal delivered by CD73 molecule to human CD45RAhiCD45ROlo (naive) CD8+ T lymphocytes.
Authors: Dianzani U , Redoglia V , Bragardo M , Attisano C , Bianchi A , Di Franco D , Ramenghi U , Wolff H , Thompson L F , Pileri A 
Published: December 2022

Abstract
CD73 is a molecule expressed by a subset of CD8+ human T lymphocytes and is involved in T cell activation. CD73 expression and function were analyzed in peripheral blood CD45RAhiCD45ROlo (naive) and CD45RAloCD45ROhi (memory) CD8+ cells. We found that CD73 was expressed by a majority of naive cells (74 +/- 12%), whereas fewer memory cells were CD73+ (29 +/- 10%). Moreover, CD73 was selectively expressed by the CD11b- subset of naive CD8+ cells, which were almost all CD73+. The same result was found on CD8+ cord blood lymphocytes, which prevalently display the naive phenotype. Naive CD8+ CD11b- cells were almost unresponsive to CD3 engagement, but this apparent anergy was completely overcome when CD3 and CD73 were simultaneously cross-linked by plastic-immobilized CD73 and CD3 mAb, showing that CD73 delivers an accessory signal that allows their activation via the CD3/TCR. This costimulatory signal was tenfold more potent than that induced by CD28 ligation. A phosphotyrosine analysis by Western blotting showed that cross-linking of CD73 induced the phosphorylation of two proteins with a molecular mass of approximately 28 and 100 kDa respectively, whereas ligation of CD3 induced phosphorylation of many substrates. When CD3 and CD73 were simultaneously triggered these substrates were hypophosphorylated. Because CD73 is linked to the cell surface by a GPI anchor, the transduction of this signal is probably mediated by a lateral interaction with transmembrane molecules. This hypothesis was assessed by cocapping, which showed that CD73 associates strongly with CD45RC, moderately with CD8, and weakly with CD3. These data suggest that CD73 signaling is coupled to both tyrosine kinase and phosphatase activities.