bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous expression of IL-4 mRNA in lymphocytes from children with atopic dermatitis
Authors: TANG M L K , KEMP A S 
Published: July 2010

SUMMARYNormal lymphocytes do not generally produce or secrete lymphokines in the resting or unstimulated state and only express or release cytokines following activation. Recently, the spontaneous production of intracellular interferon-gamma (IFN-7) and spontaneous secretion of IL-6 has been documented in patients with atopic dermatitis. These findings indicated that lymphocytes had been previously activated in vivo. Such in vivo activation may also be associated with spontaneous production of IL-4. As measurement of IL-4 secretion by immunoassay is complicated by poor sensitivity, and only provides information on the net amount of cytokine present after secretion, adsorption, consumption and degradation have occurred, IL-4 mRNA expression in peripheral blood lymphocytes from children with atopic dermatitis and controls was examined by polymerase chain reaction (PCR)-assisted mRNA amplification. Spontaneous expression of IL-4 mRNA was detected in four of eight patients with severe atopic dermatitis. Following stimulation in vitro, seven of eight atopic patients demonstrated detectable IL-4 mRNA. In comparison, no spontaneous expression of IL-4 mRNA was found in controls, and only six of 10 controls expressed IL-4 mRNA in stimulated cultures. The spontaneous expression of IL-4 mRNA in unstimulated cultures from children with atopic dermatitis supports the possibility that previous in vivo activation has occurred, and suggests that IL-4 production is increased in vivo in atopic dermatitis. This in vivo activation together with the constitutive expression of IL-4 mRNA are likely to contribute to the spontaneous in vitro production of IgE in atopic patients.
Microglial cells qualify as the stimulators of unprimed CD4+ and CD8+ T lymphocytes in the central nervous system
Authors: CASH E , ROTT O 
Published: July 2010

SUMMARYThe potential of central nervous system (CNS)-derived cells for initiating T cell responses is not known. Using the capacity of unprimed T cells to respond to allogeneic determinants on antigen presenting cells (APC). we assessed the ability of microglial cells lo act as stimulators of primary T cell responses in vitro. For this purpose, microglial cells were activated with lipopolysaccharide (LPS). interferon-gamma (IFN-γ), or by phagocytosis of progenitor oligodendrocytes and subsequently tested for their ability to induce a proliferative response of naive, resting T cells. Activated microglial cells induced a significant proliferation of virgin, alloreactive CD4+ and CD8+ T lymphocytes, with a more substantial response of highly purified CD4+ than of CD8+ expressing T cells. Phagocytosis activation was the most efficient stimulus to induce this APC competence on microglial cells. By contrast. IFN-γ pretreated. MHC-expressing astrocytes were unable to induce similar responses of alloreactive CD4+ or CD8+ T cells under the same experimental conditions. Collectively, our data suggest the role of activated microglia as the fully immunocompetent accessory cell population of the CNS.
Persistence of virus and viral genome in myocardium after Coxsackievirus B3-induced murine myocarditis
Authors: RABAUSCH-STARZ I , SCHWAIGER A , GRÜNEWALD K , MÜLLER-HERMELINK H-K , NEU N 
Published: July 2010

SUMMARYFollowing infection with Coxsackievirus B3 (CVB3). A-strain mice develop ongoing myocarditis that persists after the virus ceases to be cultivatable from heart tissue. We studied the natural history of this virus-induced but apparently autoimmune inflammation by means of in situ hybridization (ISH) and by polymerase chain reaction (PCR). Both ISH and culture allowed detection of virus up to 2 weeks post-infection in virtually all heart tissues. In contrast, PCR revealed the presence of viral genome for a substantially longer period of time, i.e. at least 34 days after CVB3 infection. Similarly, the majority of mice showed myocardial inflammation at this time point. However, the persistence of virus did not correlate with ongoing myocarditis, and vice versa. Most mice with ongoing myocarditis produced heart myosin autoantibodies, most probably as a result of tissue damage. The lack of correlation between presence of ongoing inflammation and persistence of virus supports our previous view that the late phase of CVB3-induced myocarditis is mediated by auto immunological mechanisms.
Echinococcus multilocularis: parasite-specific humoral and cellular immune response subsets in mouse strains susceptible (AKR, C57BI/6J) or ‘resistant’ (C57B1/10) to secondary alveolar echinococcosis
Authors: GOTTSTEIN B , WUNDERLIN E , TANNER I 
Published: July 2010

SUMMARYParasite-specific humoral and cell-mediated immune responses were investigated in highly susceptible (AKR and C57B1/6J) and relatively resistant (C57B1/10) mice undergoing secondary alveolar echinococcosis (infection with Echinococcus multilocularis metacestode). The parasite-specific proliferative immune response of lymph node cells upon in vitro antigen stimulation remained weak in all three mouse strains. By day 30p.i., CD4+ lymphoblast cells dominated the total population of blast cells in all three mouse strains. There was, however, an unexpectedly high proportion of CD8+ blast cells; by day 90p.i., a marked proportional increase in CD8+ cells was seen in susceptible (AKR and C57B1/6J), but not in resistant (C57B1/10) mice. Susceptible, but not resistant mice exhibited a significantly decreased responsiveness of lymph node ceils to concanavalin A (Con A) stimulation on day 90 p.i. Analysis of the humoral immune response by ELISA showed that resistance in C57B1/10 mice was associated with the ability of the host to synthesize antibodies to Em2 of the IgG3 and IgG1 isotype. Em2 is a lectin-binding carbohydrate antigen of the laminated layer. In susceptible AKR and C57B1/6J mice, low levels of antl-Em2 antibodies of the IgG2a isotype were detected. Anti-Em2 antibodies of the IgG3/lgG1 isotype, however, were absent. Differences in subclass-specific IgG responses were confirmed by immunoblot analyses. Our findings suggest that differences in antigen recognition (with respect to subsets of humoral and cellular immune components), probably controlled by non-H-2 gene(s), coupled to immune suppression modulated by CD8+ cells and/or respective cytokines, may determine susceptibility or resistance in experimental infection with E. multilocularis.
Dipeptidyl peptidase IV (DP IV) activity in serum and on lymphocytes of MRL/Mp-lpr/lprmice correlates with disease onset
Authors: KUBOTA T , IIZUKA H , BACHOVCHIN W W , STOLLAR B D 
Published: July 2010

SUMMARYDP IV (CD26), a serine protease expressed on activated T cells, participates in immune responses in vivo as well as in vitro. We measured cell surface and serum DP IV in mice of the autoimmune MRL/Mp-lpr/lpr (MRL/1) strain, which is characterized by massive T cell proliferation and production of anti-nuclear autoantibodies. The mass of inguinal lymph nodes correlated with scrum DP IV activity. Furthermore, serum DP IV activity increased markedly in parallel with the acceleration of lymph node swelling and anti-nDNA antibody production. Serum DP IV activity in 16-week-old MRL/I mice reached levels up to three times higher than those in age-matched MRL/Mp-+/+ mice or BALB/c mice. Immunohistochemical staining and flow cytometric analysis identified DV IV on surfaces of lymphocytes from the enlarged lymph nodes of MRL/1 mice. Subcutaneous injection of the mechanism-based inhibitor, Pro-boroPro, reduced protease activity in serum and cell suspensions prepared from spleen and lymph nodes, confirming the identity of the enzyme as DP IV. These results indicate that the massively accumulating lymphocytes of MRL/1 mice have a property characteristic of activated T cells, although they express little surface CD4 or CD8 and do not produce IL-2. DP IV may participate in the role these cells play in the pathogenesis of MRL/1 autoimmune disease.
Increase of circulating γ/δ T lymphocytes in the peripheral blood of patients affected by active inflammatory bowel disease
Authors: GIACOMELLI R , PARZANESE I , FRIERI G , PASSACANTANDO A , PIZZUTO F , PIMPO T , CIPRIANI P , VISCIDO A , CAPRILLI R , TONIETTI G 
Published: July 2010

SUMMARYIn order to study the role of γ/δ T cells in the pathogenesis of inflammatory bowel disease (IBD) in humans, we measured the percentage of these cells in the peripheral blood, assessed the ratio of the non-disulphide-linked (δTCS1) type of T cell receptor (TCR) in the total γ/δ T cells, studied the co-expression of γ/δ TCR and accessory molecules CDS and CD 16, and compared these data with both the type and the activity of the disease. Percentage levels and absolute numbers of γ/δ+ T cells were higher in active patients than in controls (P &lt; 0·05), mainly as a result of an increase of Vδ1+ (δTCS1) T cell subset (P &lt; 0·05). This trend was strongly retained independently of disease activity and clinical picture. An increased percentage of TCRδ1+/CD16+ cells was observed in our patients compared with controls (P &lt; 0·05). In contrast, no difference was observed as far as the TCRδ1+/CD8+ cells were concerned. These results suggest that IBD is associated with an expansion of γ/δ T cells in peripheral blood, which may play a role in the pathogenesis of these disorders.
Envelope glycoprotein (gp120) from HIV-1 enhancesMycobacterium aviumgrowth in human bronchoalveolar macrophages; an effect mediated by enhanced prostaglandin synthesis
Authors: DENIS M 
Published: July 2010

SUMMARYHuman bronchoalveolar lavage (BAL) macrophages were obtained from normal human volunteers and infected with an AIDS-associated strain of Mycobacterium avium. infected cells were exposed to purified envelope glycoprotein (gp120) from HIV-1 or to the recombinant non-glycosylated gp120 fragments PBI-RF and PBI-IIIB. Native gp120 increased Myco. avium growth in human cells from six separate donors, whereas the non-glycosylated fragments of gp120 had no such effect. Moreover, gp120 induced a substantial secretion of prostaglandin E2 (PGE2) from macrophages; inclusion of indomethacin blocked the enhanced permissiveness of infected cells treated with gp120. Soluble CD4 also neutralized the effect of gp120. Overall, these results indicate a role for gp120 in the susceptibility of AIDS patients to Myco. avium infections, mediated by an enhanced PGE2 release.
Brain-reactive autoantibodies in BB/d rats do not recognize glutamic acid decarboxylase
Authors: DAVENPORT C , LOVELL H , JAMES R F L , TODD I 
Published: July 2010

SUMMARY
The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) similar to that in humans. The most practical markers of β cell autoimmunity are circulating antibodies to islet cell components. In particular autoantibodies to the enzyme glutamic acid decarboxylase (GAD) are a common feature of IDDM development in humans. This study aims at investigating the prevalence and levels of autoantibodies in BB rats to antigens in a semipurified, GAD-enriched preparation from rat brain. Eighteen diabetes-prone BB/d rats (10 male and eight female) were tail bled weekly from age 28 days to 113 days and antibodies detected on the rat brain preparation by ELISA. Antibody levels were expressed as arbitrary units relative to a standard positive serum. Individual rats varied in the time and order of antibody appearance and IDDM onset, with the earliest occurrence being 42 days and 69 days, respectively. In some rats antibody production was maintained but declined in others. By 113 days 85% of diabetic rats had at some time been positive for autoantibodies to brain components, compared with 25% of non-diabetics (P= 0·09 by Fisher's exact test), Immunoabsorption studies using recombinant rat GAD-65 or recombinant human GAD-67 failed to inhibit the binding of BB rat sera to the original rat brain preparation. A capture ELISA using GAD-6 MoAb to capture GAD-65 from rat brain preparation or from a preparation of recombinant rat GAD-65, failed to detect anti-GAD antibodies in BB rats. Immunofluorescent staining of tissue sections showed the autoantibodies to be brain-specific, but having distinct staining patterns to the anti-GAD antibodies of Stiff Man Syndrome serum. In conclusion, BB rats possess autoantibodies reactive with rat brain antigens which may he associated with IDDM. However, these are not directed against GAD.
T cell lines recognizing the 70-kD protein of U1 small nuclear ribonucleoprotein (U1snRNP)
Authors: Fenning S , Wolff-Vorbeck G , Hackl W , Krawinkel U , LÜHrmann R , Northemann W , Peter H H , Schlesier M 
Published: July 2010

SUMMARYIn sera of patients with mixed connective tissue disease (MCTD) high titres of IgG autoantibodies to U1snRNP-specific proteins (70kD, A, C) are found, suggesting an antigen-driven and T cell-dependent process. In order to establish U1snRNP-specific T cell lines we cultured under various culture conditions mononuclear cells from MCTD patients and healthy donors with a highly purified UsnRNP preparation from HeLa cells. Nine T cell lines were established by limiting dilution cloning from two MCTD patients and five T cell lines from a healthy individual. All T cell lines expressed the TCRαβ/CD3 complex. Surprisingly, most of the T cell lines exhibited the CD8 phenotype. Irrespective of this phenotype, all T cell lines showed a proliferative response to an N-terminal pan (aa 51–195) of recombinant U1-specific 70-kD protein. One CD8+ T cell clone exhibited cytotoxic activity against an autologous B cell line pulsed with snRNP or recombinant fragments (aa 51–195 and aa 51–88). Interestingly, two T cell lines proliferated in response to four recombinant polypeptides representing different parts of the U1snRNP 70-kD protein. Since regions of sequence homology are distributed over the 70-kD molecule, it is suggested that conserved motifs may be recognized by the T cell lines.
Induction of tumour necrosis factor-alpha (TNF-α) mRNA in bladders and spleens of mice after intravesical administration of bacillus Calmette-Guérin
Authors: SHIN J S , PARK J H , KIM J D , LEE J M , KIM S J 
Published: July 2010

SUMMARYIntravesical bacillus Calmette Guérin (BCG) therapy is highly effective in the therapy of carcinoma in situ of the bladder, but the mechanism of BCG immunotherapy is not clearly understood. We studied the production of TNF-n in spleens and bladders of mice after intravesical BCG or BCG/interferon-gamma (IFN-γ) instillation. Significant change of TNF-a mRNA expression of spleens and bladders of C3H/He mice was observed after intravesical BCG instillation, although intravesical IFN-γ therapy 3 days after BCG instillation to maintain the activated state of monocyte/ macrophage lineage cells did not show a significant change of TNF-α mRNA, compared with that of BCG therapy alone. Maximal production of TNF-α mRNA in spleens of mice was seen after the first or second intravesical BCG instillation, and production of TNF-α mRNA in bladders was also increased after intravesical BCG instillation. The increment of TNF-α production by BCG stimulation in HL-60, a promyelocytic leukaemic cell line, and peripheral blood mononuclear cells in vitro may support the in vivo effect of BCG therapy on the bladder. These data show that local production of TNF-a as well as systemic production by intravesical BCG treatment may correlate with one of the mechanisms of BCG immunotherapy of superficial bladder cancer.
Presence of mRNA for interferon-gamma (IFN-γ) in blood mononuclear cells is associated with an active stage I sarcoidosis
Authors: SWIDER C , LABA A , MONIEWSKA A , GERDES J , FLAD H-D , LANGE A 
Published: July 2010

SUMMARYPeripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells obtained from sarcoidosis patients were investigated for the presence of mRNA for IFN-γ. RNA was extracted from freshly obtained cells. In 12 cases PBMC were studied and in seven cases BAL cells were also available for concomitant investigation. In eight patients mRNA for IFN-γ was present in blood and was significantly associated with stage I disease (P=0.030). By comparison, BAL cells were less frequently positive for IFN-γ transcripts (P=0.039). Only one patient had simultaneous expression of IFN-γ gene in blood and BAL cells. All other patients including four positive in blood were negative in BAL. The presence of IFN-γ transcripts in PBMC was significantly associated with the capacity of these cells to generate IFN-γ in unstimulated cultures. FBMC from patients showing IFN-γ mRNA in blood were frequently high IFN-γ producers in anti-CD3 MoAb-stimulated cultures.
Serological distinction of integral plasma membrane proteins as a class of mycobacterial antigens and their relevance for human T cell activation
Authors: Mehrotra J , Bisht D , Tiwari V D , Sinha S 
Published: July 2010

SUMMARY
This study pertains to classification and antigenic analysis of mycobacterial plasma membrane proteins in relation to human T cell proliferative responses, using a ‘fast grower’ Mycobacterium fortuitum as model. Membrane vesicles, prepared by sonication and differential centrifugation, were subjected to biphasic Triton X-1 14 extraction for isolation of integral (detergent phase) and peripheral (aqueous phase) proteins. Neither protein pool showed any appreciable overlap serologically. SDS-PAGE showed five prominent bands in peripheral and three in the integral protein pool, whereas immunoblotting with rabbit antisera identified only two major antigens (60 and 67kD) in the former and five (24, 34, 42, 51 and 54kD) in the latter, ELISA with a panel of anti-mycobacterial MoAbs revealed that nine out of 12 previously known antigens were present in the peripheral protein pool. Only two of them (33 and 40 kD) were additionally detected amongst integral proteins. The membrane-associated immunosuppressive moiety lipoarabinomannan was semiquantitatively located in aqueous phase. In bulk T cell proliferation assays, seven out of 10 subjects belonging to a ‘responder’ background (BT-BB leprosy patients and healthy contacts) showed high responses for Myco. fortuitum antigens. Proliferative response with integral proteins was comparable to that with whole membrane, hut it was significantly higher (P &lt; 0.0005) than t he response with peripheral proteins. The distinction and relevance of integral membrane proteins as a class of mycobacterial antigens make them worthy of consideration in a subunit vaccine design.
Human T cell responses to peptide epitopes of the 16-kD antigen in tuberculosis
Authors: Friscia G , Vordermeier H M , Pasvol G , Harris D P , Moreno C , Ivanyi J 
Published: July 2010

SUMMARYThe 16-kD protein constituent of the Mycobacterium tuberculosis complex has been known mainly for its prominent serological immunogenicity and species specificity in tuberculous infection. In this study, we evaluated the T cell Immune repertoire in 27 sensitized healthy subjects and 46 patients with active tuberculosis using 14 overlapping 20mer peptides spanning the entire sequence of this protein. Four of the tested peptides individually stimulated proliferation of blood mono-nuclear cells from more than 50% of healthy controls. Tuberculosis patients reacted to a narrower peptide range and with a 17-27% lower rate of responses to the four most immunogenic peptides but these differences do not distinguish in any simple way between the T cell repertoire of patients and sensitized healthy subjects. The most immunogenic peptide (91-110) was recognized by 67% of healthy subjects and by 50% of tuberculosis patients. Importantly, several non-responders to this peptide were stimulated with the other three most permissive peptides with sequences of 111 - 130,71-91 and 21-40. resulting in an overall response rate to at least one of these four peptides of 93% in healthy controls and 74% in tuberculosis patients. In view of this additive effect between the most immunogenic peptides, their combined use may achieve sufficient sensitivity in a test aimed at the specific discrimination between infected and non-infected healthy subjects. The major interest in testing with these peptides rests in their species specificity, which is not achieved using purified protein derivative (PPD).
Anti-M4 antibodies measured by a sulphite oxidase ELISA in patients with both anti-centromere and anti-M2 antibodies
Authors: Bunn CC , Mcmorrow M 
Published: July 2010

SUMMARYIn this study the clinical features of patients with a serological overlap between scleroderma and primary biliary cirrhosis (PBC) were analysed. The entity was defined by the presence of both anti-centromere antibody (ACA) and anti-mitochrondrial antibodies to the M2 antigen, pyruvate dehydrogenase. In addition the sera were assayed for anti-mitochondrial antibodies to the M4 antigen measured by an ELISA to sulphite oxidase (SO). First, anti-M2 was detected, not only in 58 out of 60 patients with PBC but also in eight out 01 61 patients with ACA. These sera, together with sera from 53 normals and 99 from patients with various connective tissue diseases were then evaluated for anti-SO. which has been proposed by Klein and Berg to be a marker of progressive liver disease. Again, a high proportion (62%) of sera from patients with PBC were positive for anti-SO. and three of the eight patients who had ACA and anti-M2 also reacted with SO. We subsequently identified and included for study a further 10 patients positive for ACA and anti-M2, making a total of 18 patients with this profile. Features of limited cutaneous scleroderma were present in 94% and evidence of liver disease in 56%. Eight out of the 18 patients had anti-SO, and of these four had PBC. two had abnormal biochemical liver function tests but two had no evidence of liver disease. These data confirm that detection of anti-SO is limited to an anti-M2 sub-population, and may be a marker for liver involvement with prognostic significance in scleroderma patients with ACA.
Expression of Fcγ and complement receptors in monocytes of X-linked agammaglobulinaemia and common variable immunodeficiency patients
Authors: Amoras A L B , Da Silva M T N , Zollner R L , Kanegane H , Miyawaki T , Vilela M M S 
Published: July 2010

SummaryRecently we reported that monocyte phagocytosis and chemotaxis are impaired in X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVI) patients. Few data exist on the in vivo expression of receptors for the constant region of immunoglobulin (IgG) (FcγR) and complement receptors (CR) in these patients. The objective of this study was to investigate the expression of FcγR and CR on monocytes from XLA and CVI patients and compare it to that of healthy controls. Whole blood samples were obtained from 10 patients with XLA, 12 with CVI and 18 healthy controls. Monocyte phenotype was determined by flow cytometry with gating on CD14+ cells. Surface expression of FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16), CR1 (CD35) and CR3 (CD11b and CD18) was measured by determination of the proportion of CD14+ cells positive for each receptor and by receptor density. Compared to controls, a significantly higher percentage of CD16 and CD35+ monocytes from XLA (P = 0·002 and P = 0·007, respectively) were observed. The relative fluorescence intensity (RFI) expression of FcyRII (CD32) and FcyRIII (CD16) were significantly lower on CVI monocytes compared to controls (P = 0·001 and P = 0·035, respectively). XLA patients, who have a reduction of Bruton's tyrosine kinase (Btk), showed normal or increased percentages of monocytes expressing Fcy and complement receptors. CVI patients, who have normal expression of Btk, showed reduced expression of CD16 and CD32 on monocytes. Inefficient chemotaxis and phagocytosis, reported previously in XLA patients, could be due to defects of cytoplasmatic transduction mechanisms.