bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased IL-10 production by stimulated whole blood cultures in primary IgA nephropathy
Authors: De Fijter J W , Daha M R , Schroeijers W E M , Van ES L A , Van Kooten C 
Published: March 2003

SUMMARYMost patients with primary IgA nephropathy (IgAN) have a significantly higher memory repertoire of IgA1-producing B lymphocytes in their bone marrow together with high plasma levels of IgA1. The connection between the mucosal immune system and the bone marrow compartment is probably based on traffic of either antigen-presenting cells (APC) or antigen-specific lymphocytes. Cytokines play an important role in the proliferation and differentiation of lymphoid cells. In order to mimic the in vivo situation as much as possible, we assessed cytokine production profiles ex vivo in 23 IgAN patients and matched controls, using lipopolysaccharide (LPS)- or phytohaemagglutinin (PHA)-stimulated whole blood (WB) cultures. Interferon-gamma (IFN-γ), IL-2, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-α) production in culture supernatants were determined by cytokine-specific ELISAs. Compared with controls, PHA-stimulated cultures resulted in significantly higher IL-10 (P &lt; 0.001), IL-2 (P &lt; 0.005) and IFN-γ (P &lt; 0.001) levels in IgAN patients, but no significant differences in TNF-α or IL-6 levels were found. In LPS-stimulated cultures, the only significant difference (P &lt; 0.001) between the two groups was the increased IL-10 production in IgAN patients. The enhanced cytokine production in stimulated WB cultures suggests altered monocyte-related T cell responses in patients with IgAN. Increased IL-10 production may eventually result in an increased number of IgA-producing B lymphocytes in the bone marrow. In addition, high levels of endogenous IL-10 may down-regulate the effector functions of monocytes, or possibly APC in general, and consequently the IgA response at the mucosal level.
Kinetics of purified protein derivative (PPD) proliferation reflects underlying suppressor mechanisms revealed by limiting dilution analysis (LDA) in patients with extrapulmonary tuberculosis (TB)
Authors: Lukey P T , Latouf S E , Ress S R 
Published: March 2003

SUMMARYMononuclear leucocytes from the blood (PBML) and effusion (EML) of patients undergoing pericardiocentesis were assayed for proliferative response to purified protein derivative of Mycobacterium tuberculosis (PPD). Of the 23 patients tested, 10 had culture-positive tuberculous effusions, while 13 had non-tuberculous aetiologies. Three different kinetic responses were identified: (i) accelerated responses (found in 70% of EML from patients with culture-positive tuberculous effusions); (ii) ‘flat’ responses (found in 10% of EML from patients with culture-positive tuberculous effusions); and (iii) normal kinetic responses. These differences in kinetic response may reflect underlying immune mechanisms important in the immunopathogenesis of TB. In order to address this possibility we performed LDA on a selection of patients with culture-positive extrapulmonary TB: three patients with accelerated responses, two with normal responses, and one with a ‘flat’ response. The results confirm the previously reported accumulation of PPD-specific responder cells in the effusion of patients with TB. Cell-mediated suppressor mechanisms (as shown by ‘V’-shaped LDA curves) were found in the blood of one patient and the effusion of another. In both cases ‘flat’ PPD-proliferative responses were observed. However, the LDA data also suggested the presence of in vivo mechanisms limiting the clonal burst size. Thus it appears that immune responses in extrapulmonary TB are influenced by an array of inhibitory mechanisms, modulation of which may influence the outcome of infection.
Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is not accompanied by enhanced production of IL-6, IL-10 or IL-12
Authors: Snijders A , Van Der Pouw Kraan T C T M , Engel M , Wormmeester J , Widjaja P , Zonneveld I M , Bos J D , Kapsenberg M L 
Published: March 2003

SUMMARYAD is associated with a bias of the T helper cells to show increased IL-4 and reduced interferon-gamma (IFN-γ) production. The production of IFN-γ and IL-4 and the development of Th cells into either high IFN-γ or high IL-4 producers is strongly influenced by factors produced by antigen-presenting cells (APC), like IL-12 and prostaglandin E2 (PGE2). IL-12 selectively enhances IFN-γ production and favours the development of IFN-γ-producing Th cells, whereas PGE2 selectively inhibits IFN-γ production by Th cells. The aim of this study was to test whether the increased IL-4/IFN-γ production ratio by Th cells in AD can be explained by an increased PGE2/IL-12 production ratio by the APC. Monocytes were used as APC source. PGE2 and IL-12 production by lipopolysaccharide (LPS)-stimulated monocytes from 12 AD patients and 12 non-atopic controls was determined using two complementary experimental systems, whole blood cultures and purified monocytes. In addition, we determined IL-6 production as a measure of monocyte activation, and IL-10 production because IL-12 production by monocytes is highly influenced by endogenously produced IL-10. The monocytes from AD patients showed normal production levels of IL-6 and IL-10, a two-fold, but non-significant decrease in IL-12 production, and a significantly (three-fold) higher PGE2 production than those from non-atopic controls. Here we show for the first time that enhanced PGE2 production by monocytes in AD is not accompanied by a general rise in cytokine production. We conclude that AD is indeed associated with an increased PGE2/IL-12 production ratio by monocytes.
cDNA cloning of a novel autoantigen targeted by a minor subset of anti-centromere antibodies
Authors: Muro Y , Yamada T , Himeno M , Sugimoto K 
Published: March 2003

SUMMARY
Using autoimmune serum from a patient with anti-centromere antibodies, we have identified and partially characterized a novel protein with a mol. wt of ≈ 27 kD (hereafter referred to as p27). A cDNA expression library was screened with this serum, and two overlapping inserts were isolated among three positive clones other than clones corresponding to centromere protein (CENP)-B and CENP-C. Analysis of the sequence showed an open reading frame of ≈ 0.6 kb encoding 199 amino acids with a predicted mol. wt of 21.5 kD. Immunoblotting analysis with bacterial recombinant p27 showed that ≈ 2% of anti-centromere antibody-positive patients had autoantibodies to p27, whereas only one of 215 autoimmune patients without anti-centromere antibodies reacted with the recombinant. All five cases with anti-p27 antibodies, who were diagnosed as having scleroderma and/or Sjögren's syndrome, showed internal organ involvement. Although affinity-purified anti-p27 human or mouse polyclonal antibodies failed to stain any cellular structures in an immunofluorescence study, the potential association of anti-p27 with anti-centromere antibodies suggests that this novel autoantigen might play a role in mitosis.
Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy family members
Authors: Kerttula T O , Holm K , Partanen J , Polvi A , Mäki M 
Published: March 2003

SUMMARY
Increased proportions of circulating antigen-primed CD45RO+ TCR γδ cells have been found in untreated CoD patients. As certain immunological features are now found in both CoD and healthy persons carrying the HLA DQ2 heterodimer, we sought to establish whether healthy members of the families of CoD patients who are positive for HLA DQ2 and also have increased densities of TCR γδ intraepithelial lymphocytes (IEL) in their small bowel mucosa have elevated levels of circulating TCR γδ memory cells. Peripheral blood T cells were analysed by flow cytometry in 22 patients with CoD and 16 healthy family members. Untreated CoD patients had higher percentages of circulating CD45RO+ TCR γδ cells and CD45RO+ Vδ1+ cells than healthy family members. On the other hand, the amount of circulating Vδ1+ lymphocytes was lower in patients with CoD compared with healthy family members. In contrast, no differences were found between HLA DQ2+ and HLA DQ2− healthy family members in respect of circulating TCR γδ cell subsets. The change in circulating TCR γδ cell subsets found in patients with CoD is thus a consequence of an ongoing immunological process which diminishes on a gluten-free diet rather than a phenomenon directly caused by DQ2. These changes in peripheral blood are not found in healthy individuals who have the same HLA alleles DQA1*0501 and DQB1*0201 encoding the HLA DQ2 and who also have increased densities of TCR γδ IEL in their otherwise normal jejunal mucosa.
Abnormal T cell responses to bacterial superantigens in Behçet's disease (BD)
Authors: Hirohata S , Hashimoto T 
Published: March 2003

SUMMARYThis study examines the nature of T cell hypersensitivity in BD. Highly purified T cells from 32 BD patients, from 29 rheumatoid arthritis (RA) patients and from 14 healthy individuals were cultured with various concentrations of Staphylococcal enterotoxins (SE) B and C1 in the presence of monocytes for 5 days, after which the production of interferon-gamma (IFN-γ) was assessed. High concentrations of SE (1 ng/ml) stimulated BD T cells as well as control T cells to produce comparably high amounts of IFN-γ, whereas low concentrations of SE (1 pg/ml) stimulated BD T cells much more effectively than normal or RA T cells. The hypersensitivity of BD T cells to low concentrations of SEC1 was restored with RA monocytes instead of BD monocytes, whereas BD monocytes could not elicit the SEC1-induced IFN-γ production of RA T cells. Moreover, there were no significant differences between BD T cells and RA T cells in monocyte-independent IFN-γ production stimulated with low or high concentrations of immobilized anti-CD3, or in the monocyte-mediated enhancement of IFN-γ production stimulated with a low concentration of immobilized anti-CD3. These results confirm that T cell hypersensitivity is not confined to certain specific antigens in BD. More importantly, the data strongly suggest that abnormalities in signal transduction triggered by perturbation of T cell receptors, but not in that induced by cross-linking of CD3 molecules nor in that delivered through costimulation molecules, play an important role in the pathogenesis of BD.
Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection
Authors: Gregorio G V , Pensati P , Iorio R , Vegnente A , Mieli-Vergani G , Vergani D 
Published: March 2003

SUMMARY
HCV infection and interferon-alpha (IFN-α) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-α cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-α, 22 untreated), tested on 165 occasions over a median of 9 months (range 5–42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-α had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-α; and (iii) IFN-α should be used cautiously in the treatment of LKM-1/HCV-positive patients.
Increase in dendritic cell numbers, their function and the proportion uninfected during AZT therapy
Authors: Gompels M , Patterson S , Roberts M S , Macatonia S E , Pinching A J , Knight S C 
Published: March 2003

SUMMARYThe effects of AZT treatment on the numbers, level of infection and function of peripheral blood dendritic cells (DC) were examined in patients with HIV infection. This was a cross-sectional study of patients before AZT treatment and up to 20 months after initiation of treatment. Numbers of DC separated by density gradients were below the normal range in patients before treatment, but increased between 3 and 12 months of treatment. The numbers of DC per provirus copy rose from around 100 cells to 5000 cells and this decrease in viral load in DC was significant between 3 and 20 months of treatment. The capacity of DC to stimulate allogeneic T cell proliferation was low before treatment and significantly higher between 6 and 12 months after the start of AZT. This study indicated that AZT treatment produced beneficial effects on DC by increasing their numbers, reducing the provirus load and increasing their function in stimulating T cells. These results support the thesis that the function of these potent antigen-presenting cells is important in development of immunological defects in AIDS, and that effects of AZT treatment on DC may provide a measure of its therapeutic effect.
Phenotypic and functional modulation of T cellsin vivoby extrathymic T cells when T cells with MHC class II disparity were injected into athymic nude mice
Authors: Tomiyama K , Watanabe H , Seki S , Ito M , Abo T 
Published: March 2003

SUMMARYTCRhigh cells are generated by the mainstream of T cell differentiation in the thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in the liver and by an alternative intrathymic pathway. It is still unknown how these T cell populations interact in vivo with each other. To investigate the interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude (B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated nude mice permitted a full expansion of TCRhigh cells which expressed the IL-2Rα+β+ phenotype, namely, they were at the most activated state. These mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor origin and such TCRhigh cells continued to have the IL-2Rα±β+ phenotype. These mice could survive but showed signs of chronic GVHD thereafter. In both situations, CD4+αβ T cells expanded irrespective of donor or recipient origin. These results suggest that TCRint cells in the recipient mice possess a regulatory function in relation to donor TCRhigh cells; as a result, fully activated TCRhigh cells acquired the IL-2Rα+β+ phenotype and injured the host, but TCRhigh cells suppressed in vivo remained as the IL-2Rα±β+ phenotype and only partially injured the host.
Effects of IL-2 therapy in asymptomatic HIV-infected individuals on proliferative responses to mitogens, recall antigens and HIV-related antigens
Authors: Kelleher A D , Roggensack M , Emery S , Carr A , French M A , Cooper D A 
Published: March 2003

AbstractThe effects of IL-2 therapy on lymphoproliferative responses to mitogens, recall antigens and HIV epitopes were studied in asymptomatic HIV-infected patients enrolled in a phase II study of intermittent continuous intravenous (CIV) IL-2 and subcutaneous infusions of polyethylene glycol-modified (PEG) IL-2. Sixteen consecutive patients randomized to receive CIV IL-2 (n = 5), PEG IL-2 (n = 7) or anti-viral therapy alone (n = 4) were studied. All patients were vaccinated with tetanus toxoid (TT) before receiving therapy. Proliferative responses to phytohaemagglutinin (PHA), soluble anti-CD3, TT, streptokinase/streptodornase (SK/SD) and 11 previously described HIV-specific T-helper epitopes from gag and env were studied at weeks 0, 16, 30 and 48. Median CD4+ lymphocyte increases of 272 and 255 CD4+ cells/μl were observed in the CIV IL-2 and PEG IL-2 groups at week 48, while decreasing by 104 cells/μl in the anti-retroviral therapy alone group. At each time point proliferative responses to PHA, anti-CD3, TT and SK/SD were not different between treatment arms. Similarly, no differences in responses to HIV epitopes were found between the groups and no new responses to HIV epitopes were detected. IL-2 therapy results in a significant increase in peripheral blood CD4+ lymphocyte count, but this increase is not associated with quantifiable improvements in lymphoproliferative responses to mitogens, recall or HIV antigens.
Iodination of human thyroglobulin (Tg) alters its immunoreactivity. II. Fine specificity of a monoclonal antibody that recognizes iodinated Tg
Authors: Saboori A M , Rose N R , Burek C L 
Published: March 2003

SUMMARYIn a previous investigation, we found that murine MoAb 42C3, raised against human Tg, recognized Tg differently depending upon its level of iodination of Tg. A possible explanation for this finding is that iodine is directly involved with the specific epitope recognized by MoAb 42C3. In the present study, we report that the binding of MoAb 42C3 to iodinated Tg is inhibited by T4, T3, reverse T3 (rT3), triiodothyroacetic acid (triac), diiodothyronine (T2), diiodotyrosine (DIT), but not by thyronine (T0) or tyrosine. The order of inhibition of these iodinated compounds is T4 &gt; T3 &gt; rT3 &gt; triac &gt; T2 &gt; DIT. The MoAb 42C3 does not have the same specificity as the T3, T4-receptor since the order of binding of these iodinated compounds on the receptor differed from the order of their inhibition of this MoAb. Monoclonal antibody 42C3 also recognized non-iodinated Tg that was subsequently iodinated in vitro. It failed to recognize another protein, bovine serum albumin, that was iodinated in vitro by the same method. These results suggest that iodinated tyrosines and thyronines determine the binding specificity of MoAb 42C3. The inhibitory effects of these compounds on MoAb 42C3 depend on their iodine content as well as location of iodine in the aromatic ring.
The murine buccal mucosa is an inductive site for priming class I-restricted CD8+ effector T cellsin vivo
Authors: Desvignes C , Estèves F , Etchart N , Bella C , Czerkinsky C , Kaiserlian D 
Published: March 2003

SUMMARYThe present study shows that Langerhans cells of the buccal mucosa and the skin share a similar phenotype, including in situ expression of MHC class II, the mannose receptor DEC-205 and CD11c, and absence of the costimulatory molecules B7.1, B7.2 and CD40 as well as Fas. Application of 2,4-dinitrofluorobenzene (DNFB) onto the buccal mucosa is associated with a rapid migration of dendritic cells (DC) to the epithelium and induction of B7.2 expression on some DC. Buccal sensitization with DNFB elicited a specific contact sensitivity (CS) in response to skin challenge, mediated by class I-restricted CD8+ effector T cells and down-regulated by class II-restricted CD4+ T cells, demonstrated by the lack of priming of class I-deficient mice and the enhanced response of class II-deficient mice, respectively. CS induced by buccal immunization is associated with priming of class I-restricted CD8+ effector T cells endowed with hapten-specific cytotoxic activity. Thus, the buccal epithelium is an inductive site, equivalent to the epidermis, for the generation of CS independent of CD4 help, and of cytotoxic T lymphocyte (CTL) responses mediated by class I-restricted CD8+ T cells. We propose that immunization through the buccal mucosa, which allows antigen presentation by epithelial DC efficient for priming systemic class I-restricted CD8+ CTL, may be a valuable approach for single-dose mucosal vaccination with subunit vaccines.
Autoimmune responses to the β cell autoantigen, insulin, and the INS VNTR-IDDM2 locus
Authors: Sarugeri E , Dozio N , Belloni C , Meschi F , Pastore M R , Bonifacio E 
Published: March 2003

SUMMARY
Type 1 diabetes is associated with autoimmunity to insulin. Genetic susceptibility to type 1 diabetes is polygenic and includes the INS VNTR-IDDM2 locus which may regulate the expression of insulin in pancreas and thymus. In order to determine whether insulin autoimmunity could be attributed to a genetic susceptibility conferred by the INS VNTR-IDDM2 locus, peripheral blood T cell proliferation to human insulin and insulin autoantibodies (IAA) was measured in patients with new onset type 1 diabetes and control subjects. IAA were detected in 21 of 53 patients and in none of 25 control subjects, while T cell responses were low (stimulation index range 0.4–7.2) and similar in both groups. Both antibody and T cell responses were higher in younger subjects and IAA were more prevalent in patients with the HLA-DR4 allele. No relationship was observed between humoral and cellular responses to insulin. No association was found between the INS VNTR-IDDM2-susceptible allele and insulin autoimmunity. Increased T cell responses and IAA were found in patients with either the diabetes-susceptible or the diabetes-protective INS VNTR-IDDM2 locus genotypes, and increased T cell responses were also found in control subjects with either susceptible or protective INS VNTR-IDDM2 locus genotypes. This study confirms that primary T cell proliferative responses to insulin are low and detectable also in control subjects. The detection of T cell proliferation and autoantibodies to insulin in subjects with and without the protective INS VNTR-IDDM2 locus genotypes does not support the hypothesis of an allele-specific capacity for tolerance induction which could determine a susceptibility to develop autoimmunity against the insulin protein and subsequently diabetes.
Existence of activated and memory CD4+ T cells in peripheral blood and their skin infiltration in CD8 deficiency
Authors: KATAMURA K , TAI G , TACHIBANA T , YAMABE H , OHMORI K , MAYUMI M , MATSUDA S , KOYASU S , FURUSHO K 
Published: March 2003

SUMMARYCD8 deficiency is a rare primary immunodeficiency caused by the defect of a tyrosine kinase, ZAP-70, which transduces signals from the T cell receptor. We report here a case of CD8 deficiency, having CD4+ T cells with a unique phenotype. The patient's T cells did not respond to anti-CD3 stimulation in vitro, suggesting that they were naive. However, many CD4+ T cells with activated and memory phenotypes, which expressed CD45RO+, HLA-DR+ and CD25+, were present in the peripheral blood, and these cells accumulated in the perivascular area of his infiltrative erythematous skin lesions. The patient's T cells could be activated by a high concentration of phytohaemagglutinin (PHA), indicating the presence of an alternate signalling pathway which bypasses ZAP-70 and activates CD4+ T cells in vivo. The origin and role of activated CD4+ T cells in the pathogenesis involved in the skin lesions are discussed.