bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human immunoglobulin production in immunodeficient mice: enhancement by immunosuppression of host andin vitroactivation of human mononuclear cells
Authors: CAVACINI L A , KENNEL M , LALLY E V , POSNER M R , QUINN A 
Published: July 2010

SUMMARYThe affect of host and donor related factors on successful cngraftmenl of human cells into mice was examined to minimize the variability lhal has been observed in successful development of human mouse chimera for the study of human disease and immune physiology and regulation. Human immunoglobulin production in severe combined immunodeficiency (SCID) mice engrafted with human peripheral blood mononuclear cells (PBMC) was augmented by immunosupprcssing recipient mice and activating donor PBMC. Immunosuppression of recipient mice with 3 Gy of γ- irradiation induced a 10-fold increase in human igG in the sera of engrafted SCID mice. Variation in production of human IgG in recipient mice correlated with preinjection phenotype and activation status of injected PBMC. Mice injected with PBMC with a low CD4/CD8 ratio (less than 0·5) produced no delectable circulating human immunoglobulin. When the CD4./CD8 ratio was greater than 1·5. human IgG was detected in sera of PBMC-recipient SCID mice. Serum IgG increased 10-fold following in vitro activation of donor PBMC with anti-CD3. IL-2 and Slaphylococcus aureus. Successful engraflment and serum IgG production was evidenced by an increase in the recovery of activated human IgG cells in the spleens of mice with maximal IgG production. Optimization of functional engraftment required modification of both the host (SCID mice) and the donor cells.
Definition of an immunodominant T cell epitope contained in the envelope gp41 sequence of HIV-1
Authors: BELL S J D , COOPER D A , KEMP B E , DOHERTY R R , PENNY R 
Published: July 2010

SUMMARYThe majority of the immunodominant amino acid sequences of HIV-I that have been characterized to date are coded for by hypervariable gene sequences. These variable sequences are however interspersed with sequences that are highly conserved between HIV strains. Immunogenic viral products with amino acid sequences that vary minimally between strains, and that consistently elicit both humoral and cellular immune responses, may be ideal for inclusion in a subunit vaccine. We studied HIV-seronegative and HIV-infected persons, classified as asymptomatic (AS), ARC or AIDS, initially, we assessed the cellular immune status of each subject from results of T cell phenotype analyses, assays for serum levels of surrogate markers of disease progression, and responses to mitogens and recall antigen. In addition, we tested whether three short synthetic peptides derived from the conserved sequences of the envelope gp 120 (aa 262–284) and gp41 (aa 579–601), and core p 17 (aa 106–125) regions of the HTLV-I MB isolate, could elicit B cell as well as T cell responses in HIV-infected subjects. Only the gp41-derived sequence was immunogenic at both B and T cell levels. To further characterize the gp41 epitope. we used a series of overlapping synthetic peptides derived from aeonserved region of the envelope gp41 (aa 572–613). We thus identified an immunodominant 12-mer peptide sequence. gp41 (8K) (aa 593–604), which consistently elicited both T cell blastogenic and B cell (antibody) responses in AS HIV-seropositive individuals but not in ARC and AIDS patients. Linear regression analysis showed that in AS persons there was a strong positive correlation (P&lt;0·0005) between the absolute CD8* T cell numbers and the magnitude of blastogenic responses to the gp41(8)(aa 593–604). Furthermore, those AS subjects with T cells that proliferated in response to this gp41 analogue also had significantly greater serum levels of antibody to the same short peptide sequence than symptomatic ARC and AIDS patients. These results suggest that cellular responses to the immunodominant and highly conserved envelope sequences of HIV-1, associated with increased CDS+ T cells, may be important in the pathogenesis of HIV disease.
Adenosine-deaminase-associated immunodeficiency. I. Differential sensitivities of lymphocyte subpopulations exposed to 2-deoxycoformycinin vivo
Authors: BAGASRA O , HOWEEDY A , POMERANTZ R J 
Published: July 2010

SUMMARYIn order to obtain a better understanding of the degree of immune dysfunctions caused by the absence of adenosine deaminase, we gave a single i.p. injection of 2′-deoxycoformycin (2-dcf), a potent inhibitor of the enzyme ADA at various doses into adult Syrian hamsters. These animals were examined for their ability to mount primary in vivo antibody responses to helper T cell dependent (Th-d) and helper T cell independent (Th-ind) antigens. Hamsters treated with 0·5 mg/kg of 2-dcf mounted enhanced splenic plaque-forming cell (PFC) responses to sheep erythrocytes, a Th-d antigen, and to pneumococcal polysaccharide type III (SIII), a Th-ind antigen. Treatment of animals with 1·0 mg/kg of 2-dcf resulted in a significantly depressed (P &lt; 0·001) PFC response to Th-d antigen, but a further enhanced response to Th-ind antigen. One mechanism which may be responsible for such a dichotomous response to these two types of antigens was selective dysfunction of T cell subpopulations. At higher doses (1·5–4·0 mg/kg), PFC responses to both types of antigens were significantly suppressed. Immunoenhancement at low doses of 2-def was attributed to an increased susceptibility of T suppressor cells to 2-dcf. This hypothesis was confirmed by priming the 2-dcf-treated animals with low-dose Th-ind antigens. These animals failed to induce low-dose tolerance by stimulation of antigen-specific suppressor T cell subsets. At low doses, B cells and T helper cell functions were found to be intact, as further confirmed by priming the animals with the carrier keyhole limpet haemocyanin (KLH) and challenging with trinitrophenyl-KLH. This dose-dependent selective susceptibility of various T cell subpopulations and B cells may explain the heterogeneity of clinical, biochemical and immunological parameters observed in children with ADA deficiency severe combined immunodeficiency.
Epitope-specific induction of mesangial lesions with proteinuria by a MoAb against mesangial cell surface antigen
Authors: KAWACHI H , ORIKASA M , MATSUI K , IWANAGA T , TOYABE S , OITE T , SHIMIZU F 
Published: July 2010

SUMMARYA MoAb 1–22–3 (igG3) was produced in mice immunized with rat glomeruli. A blotting study indicated the antigen molecule recognized by this MoAb has a molecular weight of about 25 kD, which is the same as that of the Thy 1.1 molecule. This MoAb is capable of inducing the morphological changes similar to those induced by anti-thymocyte serum or the anti-Thy 1.1 MoAb, ER4 and massive proteinuria in rats by a single i.v. injection. Proteinuria started immediately after MoAb 1–22–3 injection and peaked on day 5. Reaction products were detected by immunoelectron microscopy in vitro on the limited mesangiai cell surface facing endothelial cells and in vivo in partially lysed mesangial cells 30 min alter injection. Unlike the proteinuria-inducing MoAb ER4, reactivity of MoAb 1–22–3 was detected neither on endothelial cells, epithelial cells, nor along the glomerular basement membrane in vivo and in vitro. There is a difference in reactivity toward guinea-pig and rabbit materials between MoAb 1–22–3 and the commercial anti-Thy 1.1 MoAb(OX7). The antigenic determinant of MoAb 1–22–3 is concluded to be a new epitope and only the binding of MoAb 1–22–3 to this epitope proved to lead to an abnormal increase of glomerular capillary wall permeability.
Increased frequency of the long (S) allotype of CR1 (the C3b/C4b receptor, CD35) in patients with systemic lupus erythematosus
Authors: CORNILLET P , GREDY P , PENNAFORTE J L , MEYER O , KAZATCHKINE M D , COHEN J H M 
Published: July 2010

SUMMARYThe allotypic forms of the C3b/C4b receptor (CR1, CD35) differ in length, in the number of expressed C3b binding sites and thus in their ability to mediate the processing of circulating C3- and C4-bearing immune complexes. We have used a combination of three informative restriction fragment length polymorphisms (RFLPs) to assess the frequencies of the F (most frequent allele comprised of four long homologous repeats (LHR)), S (five LHR) and F′ (three LHR) alleles of the C3b/C4b receptor (CR1, CD35) in a French population of patients with systemic lupus erythematosus (SLE) (n= 63) and healthy controls (n= 158). A significantly higher frequency of the S phenotype was observed among patients (51%) as compared with controls (26%). The F′allele was found in 2/61 patients and 1/85 healthy controls, indicating the rare occurrence of the short CR1 allele in SLE. This allele is also extremely rare in the normal population. The overrepresentation of the S long allele among patients is indicative of a genetic linkage between CR1 and susceptibility to SLE.
IgG antibodies from patients with primary Sjögren's syndrome and systemic lupus erythematosus recognize different epitopes in 60-kD SSA/Ro protein
Authors: BARAKAT S , MEYER O , TORTEROTOT F , YOUINOU P , BRIAND J P , KAHN M F , MULLER S 
Published: July 2010

SUMMARYFive synthetic peptides corresponding to the N-, the C- and a central domain in 60-kD SSA/Ro protein were prepared and tested with sera from 112 patients with systemic lupus erythematosus (SLE), 55 with primary Sjögren's syndrome (pSS) and 29 with rheumatoid arthritis. Among these five fragments, one representing residues 21-41, was recognized by antibodies in 57% of pSS patients. Interestingly, this peptide was recognized by only a few (≤7%) of SLE sera, while 63% of pSS sera and 46% of SLE sera tested in parallel possessed antibodies reacting in ELISA with purified 60-kD SSA protein. The ELISA results were compared with the pattern of reactivity obtained in immunodiffusion and immunoblotting. The results indicate that the sensitivity of ELISA using peptide 21-41 and pSS sera was in the same range as immunoblotting and higher than immunodiffusion. Thus the peptide 21-41 proved useful for the detection of anti-SSA antibodies in the sera of patients with pSS. Furthermore, a positive ELISA using peptide 21–41 could be of potential use to discriminate pSS with systemic features from SLE. The fact that peptide 21–41 is recognized by antibodies in pSS but only by very few SLE sera implies that different mechanisms are involved in the anti-SSA immune response in these two autoimmune diseases.
ANCA and associated diseases: immunodiagnostic and pathogenetic aspects
Authors: GROSS W L , SCHMITT W H , CSERNOK E 
Published: July 2010

SUMMARY
The past decade has seen an explosion of data on the new group of autoantibodies known collectively as ANCA (anti-neutrophil cytoplasmic antibodies). ANCA are specific for granule proteins of granulocytes and monocytes and induce distinct fluorescence patterns, e.g. the cytoplasmic (classic) cANCA and the perinuclear pANCA. cANCA is induced by antibodies directed against Proteinase 3 (PR3; PR3-ANCA) in about 90% of all ANCA-positive sera, and pANCA is induced by antibodies against myeloperoxidase (MPO; MPO-ANCA) in about 40%. A further staining pattern, which does not have a clear cut association with a distinct granule protein, is sometimes seen in chronic inflammatory bowel diseases. PR3-ANCA are serological markers for Wegener's granulomatosis (WG) and MPO-ANCA are associated with certain subtypes of primary vasculitides. Evidence exists that both the autoantigen and ANCA participate in the pathogenesis of at least the group of ‘ANCA-associated vasculitides’.
Comparative antibody response to salmonella antigens in genetically resistant and susceptible mice
Authors: XU H R , TAN Y Y , HSU H S , MONCURE C W , WANG X M 
Published: July 2010

SUMMARYThe ELISA was used to titrate the antibody response in mice inoculated with salmonella antigens. The genetically resistant A/J and susceptible C57BL/6J mice were either infected with the virulent or the avirulent Salmonella typhimurium. Alternatively, they were inoculated either once or twice with the heat-killed salmonella vaccine. No appreciable difference could be detected in the relative ability of these two strains of mice to produce antibodies against the lipopolysaccharide antigens of this pathogen under these four conditions.
Synovial fluid cells in juvenile arthritis: evidence of selective T cell migration to inflamed tissue
Authors: SILVERMAN E D , ISACOVICS B , PETSCHE D , LAXER R M 
Published: July 2010

SUMMARYThe perpetuation of chronic synovitis in juvenile arthritis (JA) is a complex interaction of local and systemic regulatory mechanism. We examined the cell surface phenotypc of synovial fluid cells and peripheral blood lymphocytes from 15 patients with J A to better understand the mechanism of local inflammation. Synovial fluid and peripheral blood mononuclcar cells were analysed for cell surface expression of CD2, CD3, CD4, CD8, CD19, CD25, CD29, CD45R and Ia using flow cytometry. We found a very low percentage of B cells with a concomitant increase of T cells in synovial fluid as compared with peripheral blood. A large percentage of the synovial fluid T cells were HLA-DR+.or activated T cells, and there was a relative decrease in CD4+ cells in synovial fluid as compared with peripheral blood. There was only a minimal increase in CD25+ synovial fluid cells. The synovial fluid CD4+ cells were mainly of the CD2high. CD29+, CD45RO phenotype. This CD4 phenotype found on synovial fluid cells from patients with JA and in particular the CD29 cell surface marker, which recognizes a common β-chain of adhesion molecules, is associated with binding to extracellular matrix proteins and is also associated with “primed” T cells. Our results demonstrated the presence of T cells which either selectively migrate to synovium and synovial fluid or are activated in situ in the joint.
Extracellular acidic pH modulates oxygen-dependent cytotoxic responses mediated by polymorphonuclear leucocytes and monocytes
Authors: GEFFNER J R , TREVANI A S , MINNUCCI F , PALERMO M S , MAUGERI N , ISTURIZ M A 
Published: July 2010

SUMMARYIn the present study, we compared the ability of human neutrophils and monocytes to display oxygen-dependent cytotoxic responses at pH 7.4 and 6.2. Our results show that cytotoxicity induced by immune complexes (IC), zymosan, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A) were markedly increased when they were carried out at pH 6.2 instead of pH 7.4. Cytotoxicity induced by phorbol myristate acetate (PMA), on the contrary, was significantly decreased at pH 6.2. It is noteworthy that cytotoxic responses induced by IC, zymosan and Con A were also increased when, 2 h after effector cell stimulation at pH 6.2, cytotoxicity was measured at pH 7.4. Finally, when we examined possible mechanisms involved in the augmentation of cytotoxicity, we observed that the oxidative response of IC-stimulated neutrophils, measured as chemiluminescence emission, was not increased at pH 6.2, on the contrary, it was significantly decreased. The relevance of these results is discussed.
Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers
Authors: DAUCHEL H , JOLY P , DELPECH A , THOMINE E , SAUGER E , LOET X L E , LAURET H , TRON F , EONTAINE M , RIPOCHE J 
Published: July 2010

SUMMARYWe have studied complement activation both in plasma samples and In lesional skin from palients with leukocytoclaslic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers. C3d,g and fhe terminal complement complex (TCC) in plasma, showed lhal their levels were significantly increased in 66% and 55% of the patienis, respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, Clq, C4and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were signifieantly eorrelated. Importantly, a signifieant correlation was found between the severity of the vasculitis and both C3d,g and TCC plasma levels. Immunofluorescence studies of skin biopsy specimens demonstrated simultaneous presence of peri vascular dermal deposits of C3d,g and TCC in lesional skin from 96 Mi and 80% respectively of the patients (n= 25). There was a significant eorrelation between the intensity of the deposits of bolh markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits, Immunofluorescence studies at the epidermal basemenl membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presenee of both C3d,g and clusterin-associatcd TCC perivascular deposits suggests an intervention of a regulatory mechanism of local complement activation in LCV. Einally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV.
Cytochrome P450IID6 recognized by LKMl antibody is not exposed on the surface of hepatocytes
Authors: YAMAMOTO A M , MURA C , DE LEMOS-CHIARANDINI C , KRISHNAMOORTHY R , ALVAREZ F 
Published: July 2010

SUMMARY
LKM1 autoantibody, directed againsl P450IID6, is accepted as a marker of a particular type of autoimmune hepatitis, but its role in the pathogenesisof the disease is controversial. Localisation of P450IID6 on the cell surface of rat hepatocytes was previously reported, suggesting that membranebound P450IID6 could be the target of LKM 1 antibodies, thus allowing immune lysis of hepatocytes. The objective of the present study was to determine, using various methods, the cell localization of P450IID6 in human and rat hepatocytes. Incubation of rat and human hepalocytes with LKMI-positive serum showed slight, if any. cell membrane staining using immunofluorcscencc. immunoperoxidase and immunoelectron microscopic sttidies. No staining of the plasma membrane of human hepatocytes was observed when incubations were earried out with imniunoaffinity-purificd antibody directed against peptide254–271, the main epitope of P450IID6 recognized by all LKMl sera tested. Chinese hamsler ovary cells, transfected with the complete P450IID6 cDNA and incubated with the supernatant from a B cell lymphoblastoid cell line prepared with the lymphocytes of a LKMI-positive patient, did not show any staining of the cell surface by immunofluorescence. Incubation of rat microsomal fraction vesicles with LKMl-positive serum, followed by prolein A-gold immunoelectron microscopy, displayed a staining of almost all vesicles, confirming that P450IID6 is present on the cyloplasmic side of the microsomal membrane, which makes it unable to be expressed on the ceil surface even if it were transported from the endoplasmic reticulum (ER). Sulpho NHS Biolin labelling of rat hepatocyte cell membranes did nol show the presence of a 50-kD molecule that could have reacted with LKMl antibody. DNA sequencing of exon 1 of the CYP2D6 gene of a patient positive for LKM l antibody did not show any difference from that of the normal published sequence of the gene. This does not favour an alteration of the NH2 terminal sequence of the P450IID6 molecule that could explain a translocation of the molecule to the luminal side of the ER, allowing its expression on the ceil surface. These results indicate that, in all likelihood. P450IID6 molecule is not present on the cell surface of normal rat and human hepatocytes. Other mechanisms than antibody-mediated cell lysis directed against membrane P450IID6 antigenic determinants must be found to account for the destruction of hepatocytes observed in this disease.
Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice
Authors: RUF J , FERRAND M , DURAND-GORDE J M , DE MICCO C , CARAYON P 
Published: July 2010

SUMMARY
Thyroglobulin (TG) and thyroperoxidase (TPO), both involved in thyroid hormone synthesis, represent major autoantigens in thyroid autoimmune disease. Despite numerous studies, the emergence, pathophysiological significance and role of autoantibodies to TG and TPO remain elusive. The recent identification of a new category of thyroid-specific autoantibody interacting with both TG and TPO (TGPO autoantibodies) offers a new opportunity in the study of thyroid autoimmunity. To gain a better insight into the significance of these TGPO autoantibodies, measurement in individual samples appeared necessary. The unique property of TGPO autoantibodies, simultaneous binding to TG and TPO, was used to set up a sandwich method which combined coated TG and radio-iodinatcd TPO. This method was found to be strictly specific for TGPO autoantibodies and sensitive enough to assay TGPO autoantibodies in serum. In humans, TGPO autoantibodies were found in most of the sera with high TG and TPO autoantibody titres, but not in sera negative for TG autoantibodies, whatever the TPO autoantibody litre. Furthermore, high TGPO autoantibody litres were found in sera strongly cytotoxic for cultured porcine thyroid cells. However, significant correlation of TGPO autoantibody titre was observed neither with TG and TPO autoantibody titres (n=48) nor with complement-dependent cytotoxicity (n= 50). TGPO antibody assay was also performed in individual plasma of CBA/J mice immunized with either human TG (n= 6) or human TPO (n= 6). Immunization with TG induced high levels of not only TG but also TGPO antibodies, which exhibited a strong reactivity for TPO and whose binding to TG and TPO was fully inhibited by TG. In contrast, immunization with TPO induced high levels of only specific TPO antibodies accompanied by low levels of specific TG antibodies. In this case TGPO antibodies were not detected. Of note, TG- and TPO-immunized mice mounted an immune response against their own TG, but did not exhibit histological signs of thyroiditis. Large panels of TG and TPO MoAbs were also investigated with this method: 18/25 TG MoAbs and only 1/13 TPO MoAbs were found cross-reactive. Taken together, these data provide evidence that TGPO antibodies are effectively present in individual patients and TG-immunized mice, are different from specific TG and TPO antibodies, and may derive from natural B cell repertoire by autoimmune processes involving TG and not TPO.