bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell regulation of the chronic peritoneal neutrophilia during mycobacterial infections
Authors: APPELBERG R 
Published: July 2010

SUMMARYIntraperitoneal infection of mice with mycobacteria induces the persistent mobilization of neutrophils to the infected peritoneal cavities. The recruitment of the neutrophils was mediated by the immune system since it was enhanced by immunization and reduced in T cell-deficient nude and SCID mice. Anti-mitotic treatments with cyclophosphamide or X-rays led to a reduction in the number of mononuclear cells in the peritoneal cavity of infected mice, followed by a reduction in neutrophil numbers despite the presence of a normal circulating pool of neutrophils. The depletion of T cells with antibodies during mycobacterial i.p. infection led to a reduction in the number of neutrophils. Such a reduction was more extensive if the antibodies were administered early. Our data suggest that T cells are partially involved in the direct recruitment of neutrophils during chronic mycobacteriosis but they also play a role in the priming of other cell types for the mobilization of these phagocytes.
Comparison of the properties of the CsA analogs monoacetyl CyC (o-acetyl-threonine2 cyclosporin) and methyl-alanyl CsA (N-methyl-L-alanyl6 cyclosporin); monoacetyl cyclosporin is immunosuppressive without binding to cyclophilin
Authors: EL ROUBY S , SHI Y , REEM G H 
Published: July 2010

SUMMARYCyclosporin (CsA) is an immunosuppressant which binds to cyclophilin (Cyp). The relationship between Cyp binding and immunosuppression has been questioned since one of the analogs of CsA, N-methyl-L-alanyl6 cyclosporin (methyl-atanyl CsA) binds to Cyp but is not immunosuppressive. We compared the immunosuppressive properties of CsA, methyl-alanyl CsA and o-acetyl-threonine2 cyclosporin (monoacetyl CyC), since monoacetyl CyC does not bind to Cyp when tested in cell-free assays and its immunosuppressive properties had not been tested. Cyp is a peptidyl-prolyl isomerase which is abundant in all human tissues, yet the activities of CsA are mostly confined to inhibition of T cell and thymocyte activation, and to neuro- and nephro-toxicity and are independent of inhibition of the isomerase. Activation of thymocytes and of T cells is regulated by the binding of a nuclear factor(s) (NFs) to the NF-AT region (– 285 to – 255) of the IL-2 promoter. We studied inhibition of binding to the NF-AT region of NFs derived from primary cultures of thymocytes treated with CsA or its analogs. In addition, we compared the effect of CsA and its analogs on the expression of the IL-2 gene in a stably transfected Jurkat-cell line (Fgl 5) which contains three copies of NF-AT and the reporter enzyme β-galactosidase; and on inhibition of proliferation induced by concanavalin A(Con A) or IL-2. We found that monoacetyl CyC which does not bind to Cyp is immunosuppressive by our criteria when tested in cultured cells due to either a different mechanism of action or to metabolic activation.
CD3+ CD57+ lymphocytes are not likely to be involved in antigen-specific rejection processes in long-term allograft recipients
Authors: REIPERT B , SCHEUCH C H , LUKOWSKY A , REINKE P , FIETZE E , DÖCKE W D , STAFFA G , CZERLINKSI S , HETZER R , VOLK H D 
Published: July 2010

SUMMARYCytofluorometric investigation of peripheral blood lymphocytes in 380 long-term (&gt; 1 year post-transplantation) allograft recipients showed a significant increase in the proportion of CD3+57+ lymphocytes (&gt; 20%) in 20% of patients with renal allografts, 66% of patients with cardiac allografts and 44% of patients with liver allografts. Most of these CD3+ 57+ cells expressed the CD8 antigen and a variable proportion the HLA-DR antigen. A retrospective analysis showed a poorer prognosis for the clinical outcome in those patients with elevated numbers of CD3+57+ cells in peripheral blood. However, CD57+ lymphocytes could rarely be detected in renal infiltrates by immunohistology. Using the Southern blot technique to analyse the T cell receptor rearrangement of separated CD57+ cells, no clonal or oligoclonal expansion of T cell clones could be detected. Nevertheless, there might be a bias towards the use of particular TCR-Vβ gene families in at least some patients, as shown by analysis with monoclonal antibodies. In summary, CD57+ T cells are not likely to be directly involved in the rejection process. The data support the idea of a polyclonal and/or superantigendriven expansion, but not of an antigen-driven expansion of these cells.
T cell redistribution kinetics after secondary infection of BALB/c mice with respiratory syncytial virus
Authors: KIMPEN J L L , OGRA P L 
Published: July 2010

SUMMARYBALB/c mice were infected intranasally with live respiratory syncytial virus (RSV) and reinfected 4 weeks later. At regular intervals thereafter groups of animals were killed and T cell subsets were determined in blood, spleen and bronchoalveolar lavage (BAL) with flow cytometry employing T cell subset-specific MoAbs. Total lymphocyte counts in the peripheral blood decreased 1–3 days after infection, returning to preinfection levels on day 8 (P= 0.0111). Simultaneously, a marked increase of lymphocytes was noted in the BAL, reaching a maximum at day 8 (P &lt; 0.0001). Both CD4+ and CD8 + T cells decreased in the blood on day 1–3 (P &lt; 0.0097 and P = 0.003 respectively), and increased in the BAL progressively towards a maximum at day 8 (P &lt; 0.0001). In BAL, CD4+ cells increased 35-fold and CD8+ cells 27-fold during the first week after reinfection. On the other hand, in the spleen a significant decline of CD4+ and CD8+ cells was noted 1 day post-infection (P= 0.0002). It is concluded that a strong T cell redistribution response among systemic and mucosal tissues occurs after reinfection with RSV. The kinetics of this response differ both quantitatively and qualitatively from the T cell response after primary infection. The magnitude of cell traffic is more pronounced in blood, spleen and BAL than after primary infection. CD4+ T cells are more intensively distributed to the lungs than after primary infection.
No restriction of intrathyroidal T cell receptor Vα families in the thyroid of Graves' disease
Authors: McINTOSH R S , WATSON P F , PICKERILL A P , DAVIES R , WEETMAN A P 
Published: July 2010

SUMMARYRecently it has been reported that the intrathyroidal T cells in Graves'disease display restriction in Vα T cell receptor (TcR) gene family usage, although this is not found with TcR Vβ gene families in the same individuals. We have performed a qualitative analysis of TcR Vα family usage in 12 patients with Graves'disease by reverse transcription and polymerase chain reaction (PCR) amplification of RNA extracted from isolated, unstimulated intrathyroidal lymphocytes and from snap-frozen whole thyroid specimens. No restriction was observed, with 10–15 Vα gene families being amplified in all cases. The pattern of usage was similar to that in peripheral blood lymphocytes derived from normal subjects (n = 3) and from patients with Graves'disease (n = 3), as well as that present in the thyroids of patients with non-autoimmune toxic multinodular goitre (n = 4). These results indicated that there is no marked restriction of the unselected intrathyroidal T cell population in patients with Graves'disease who have been treated with antithyroid drugs.
High frequency of spontaneous interferon-gamma-producing cells in human tonsils: role of local accessory cells and soluble factors
Authors: QUIDING M , GRANSTRÖM G , NORDSTRÖM I , FERRUA B , HOLMGREN J , CZERKINSKY C 
Published: July 2010

SUMMARYThe frequency of mononuclear cells (MNC) spontaneously secreting interferon-gamma (IFN-γ) has been examined in freshly isolated cell suspensions from human palatine tonsils. Two-site reverse enzyme-linked immunospot (ELISPOT) analyses, involving short term (20 h) incubation of MNC in the absence of any added exogenous stimulus, revealed that tonsillar MNC suspensions contain exceptionally large numbers of cells secreting IFN-γ. No significant differences were observed when comparing the frequency of IFN-γ-producing cells between cell suspensions obtained from hyperplastic and tonsillitis specimens. Cell-sorting experiments disclosed that spontaneous tonsillar IFN-y production was essentially contributed by CD4+ T cells, and required the presence of accessory cells and/or soluble factors to be detected. Thus, depletion of plastic adherent cells or monocytcs from the tonsillar MNC suspensions resulted in reduced numbers of detectable IFN-γ-secreting cells. Addition of very small numbers of autologous monocytes restored spontaneous IFN-γ production in tonsillar MNC cultures depleted of monocytes. Neutralization of endogenous IL-1β and IL-2, as well as blocking of the IL-2 receptor, also decreased IFN-γ production from unfractionated tonsillar cells. Addition of exogenous IL-1β restored IFN-γ production in cultures of tonsillar MNC depleted of plastic adherent cells. Furthermore, IL-1β synergized with IL-2 by increasing intracellular as well as cell-free levels of IFN-γ in cultures of unfractionated tonsillar MNC. This study further establishes that the tonsils are highly active immunological organs containing large numbers of T cells spontaneously producing IFN-γ whose detection is contingent upon the presence of functional accessory cells. It also demonstrates that concomitant production of IL-1β and IL-2 occurs in tonsils and is necessary to maintain ongoing synthesis and extracellular accumulation of IFN-γ in these organs.
Increased IL-6 gene expression and production in patients with common variable immunodeficiency
Authors: PANDOLFI F , PAGANELLI R , OLIVA A , QUINTI I , POLIDORI V , FANALES-BELASIO E , GUERRA E , AIUTI F 
Published: July 2010

SUMMARYWe have studied IL-6 gene expression and production by in vitro stimulated peripheral blood mononuclear cells (PBMC) isolated from common variable immunodeficiency (CVI) patients. A strong hybridization signal for the IL-6 probe was observed in mRNA extracted from phyto-haemagglutinin (PHA)- and PHA/phorbol myristate acetate (PMA)-stimulated PBMC from most of 12 CVI patients analysed. IL-6 production by PHA-stimulated PBMC from 28 CVI patients was evaluated in ELISA and found to be significantly (P &lt; 0.0001) higher than in normal controls. IL-6 production, however, did not correlate with the lymphocyte populations examined, nor with the absolute number of monocytes. We have also showed that IL-6 was able to increase IgM secretion by several Epstein Barr virus (EBV)-transformcd cell lines derived from both normal donors and CVI patients, but it failed to modify substantially the amounts of IgM and IgG produced in vitro by PBMC derived from CVI patients and activated with pokeweed mitogen (PWM) or anti-IgM. Our data indicate that IL-6 gene expression and production is increased in CVI, but CVI cells do not respond to IL-6 with increased production of immunoglobulin.
Increased epithelial expression of HLA-DQ and HLA-DP molecules in salivary glands from patients with Sjogren's syndrome compared with obstructive sialadenitis
Authors: THRANE P S , HALSTENSEN T S , HAANAES H R , BRANDTZAEG P 
Published: July 2010

SUMMARYSalivary gland specimens from 10 patients with primary Sjogren's syndrome (pSS) were examined by two-colour immunofluorescencc with various combinations of monoclonal and polyclonal antibody reagents of the following specificities: human leucocyte antigen (HLA) class I and II (DR, DP and DQ). CD3, CD45 (leucocyte common antigen), various cytokeratins, and factor VHI-related antigen. Tissue specimens from 10 normal glands and 10 glands with obstructive sialadenitis (no known autoimmunity) served as controls. Only some intercalated ducts and scattered acini of the normal major glands expressed HLA class II determinants (&lt; 5% of total epithelial area); the relative proportion of positive elements indicated differential expression (DR&gt; DP&gt; DQ). SS glands contained substantial T cell infiltrates and increased numbers of activated (DR+) T cells; adjacent epithelium showed extensive differential expression of HLA class 11 determinants (DR&gt; DP&gt; DQ). Glands with obstructive sialadenitis showed similarly increased epithelial expression of HLA-DR but with surprisingly small amounts of concomitant H LA-DP and -DQ expression. Epithelial HLA class II expression probably depends on cytokines as an inductive event, which is not unique for SS but particularly prominent in this disorder. Our results suggest that epithelial expression of HLA-DP or -DQ, rather than -DR. might be a prerequisite for the autoimmune process of SS to develop in genetically susceptible individuals.
Lupus autoantibodies discriminate between the highly homologous Sm polypeptides B/B' and SmN by binding an epitope restricted to B/B'
Authors: HUNTRISS J D , LATCHMAN D S , WILLIAMS D G 
Published: July 2010

SUMMARYThe ubiquitous Sm polypeptides B/B’ (28 and 29 kD) and the highly homologous tissue-specific Sm N polypeptide (29 kD) share several autoepitopes recognized by systemic lupus crythematosus (SLE) sera. Previous studies on the antigenicity of nuclear antigens recognized by human autoantibodies have not discriminated between ubiquitous and tissue-specific forms. We set out to examine whether a tissue-specific nuclear antigen, Sm N. is autoantigenic in SLE by comparing the immunoreactivity of the most unique sequences in this polypeptide. Synthetic peptides from the two regions of least sequence homology that occur between Sm N and Sm B/B', a dodccamer (amino acid residues 179–190 containing five substitutions) and an undecamer (residues 203–213 containing four substitutions) were coupled to a carrier protein. These conjugates were used to quantify IgG anti-peptide antibodies in sera from patients with SLE. Of 43 sera with anti-Sm specificity, six bound to the B/B’ 179-190 peptide but not to the N version. None of 17 anti-Sm-negative SLE sera bound these peplides. The second region of least sequence homology between N and B/B’ (203–213) was not antigenic. Our data suggest that a subset of SLE patients with anti-Sm reactivity have IgG autoantibodies capable of discriminating between Sm N and SmB/B' polypeptides by binding a previously unreported SmB/B'-specific autoepitope. The data also indicate that brain and heart-specific anti-Sm antibodies do not exist in SLE sera, suggesting that these tissues do not participate in the induction or maintenance of the autoimmune anii-Sm response.
Time-course of adhesion molecule expression in rectal mucosa of gluten-sensitive subjects after gluten challenge
Authors: ENSARI A , AGER A , MARSH M N , MORGAN S , MORIARTY K J 
Published: July 2010

SUMMARYAdhesive interactions between endothelium and circulating ceils, such as monocytes, neutrophils and lymphocytes, are crucial for localizing the inflammatory response. We investigated the inflammatory response of rectal mucosa to local gluten challenge as a dynamic model of antigen-induced tissue injury, during which the expression of adhesion molecules on leucocytes and endothelial cells could be sequentially observed. Expression of ELAM-I, lCAM-1 and VCAM-1 was monitored in 10 treated and eight untreated patients with gluten sensitivity (eoeliac disease), and in five disease controls for up to 4 h (short challenge), while a further seven treated coeliacs were monitored for up to 24 h (Iongchallenge) following reetal gluten challenge. In the former, Ihc expression of VCAM-1 and ELAM-I was significantly raised 4 h after gluten challenge compared with controls, VCAM-1 and ELAM-l expression was also increased in mucosac of treated patients. but to a lesser extent, VCAM-1 expression continued to increase for up to 24 h after gluten, while ELAM-l had begun to wane by 4 h, reaehing basal levels by 24 h, In eontrast, the expression of ICAM-1 did not change in any of the disease groups studied. These findings relate to significant increases in lymphocytes (CD3+ cells) after 8 h, and neutrophils (CD15+ cells) after 4h in the lamina propria. This approach has permitted novel studies of the infiammatory response to a defined antigen in sensitized (gluten-sensitive) human patients.
The human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation
Authors: WONG F S , HIBBERD M L , WEN L , MILLWARD B A , DEMAINF A G 
Published: July 2010

SUMMARYMilogen stimulation of T cells in vitro has been employed in the analysis of the T cell antigen receptor (TCR) repertoire and as a method of generating T cell lines and clones. It has been suspected for some time that mitogen stimulation may bias the repertoire. We have addressed this problem employing a semi-quantitative technique utilizing the polymerase chain reaction (PCR) and flow cytometry. Using this PCR method and a panel of primers to 22 Vβ subgroups, the Vβ repertoire of both unstimulated and phytohaemagglulinin (PHA)-stimulated peripheral T cells from eight healthy individuals was investigated. The samples were also analysed by flow cytometry using anti-Vβ2, Vβ5 and Vβ8 MoAbs. A significant increase in the expression of Vβ6, Vβ7.2 and Vβ 10.1 was found in all eight samples of PHA-stimulated T cells compared with unstimulatcd T cells using the PCR method. In contrast, no differences were found between unstimulaled and PHA-stimulated T cells by flow cytometry. These results question the validity of using milogen-stimulated T cells to investigate TCR gene usage.
Expression of glutamic acid decarboxylase (GAD) in the α, β and δ cells of normal and diabetic pancreas: implications for the pathogenesis of type I diabetes
Authors: VIVES-PI M , SOMOZA N , VARGAS F , ARMENGOL P , SARRI Y , WU J Y , PUJOL-BORRELL R 
Published: July 2010

SUMMARY
One of the paradoxes of insulin-dependent diabetes mellitus is that the destruction of the pancreatic islets’ endocrine cells is restricted to the insulin-producing β cells, whereas the main autoantibodies, islet cell antibodies (ICA), are directed against all endocrine islet cells. GAD has recently been proposed as the main target of the humoral and cellular autoimmune attack to the islets, and since in rat pancreas this enzyme was expressed only in the β cells, this provided an explanation for the cell specificity of the destructive process. The finding of GAD-positive cells in the islets of two diabetic patients, one of whom had completely lost the β cells, led us to study in detail thedistribution of GAD in normal human islet ceils using a panel of GAD aniiscra and the double indirect immunofluorescence technique on cryostat sections, monolayer cultures and cytosmears. The results showed that GAD is present not only in the cytoplasm of β cells but also in 69% of the α and 27% of the δ cells. GAD was not present, however, on the surface of the islet cells. These results suggest that the cellular distribution of GADcan not by itself explain the selectivity of β cell destruction in insulin-dependent diabetes mellitus.
Pinealectomy ameliorates collagen II-induced arthritis in mice
Authors: HANSSON I , HOLMDAHL R , MATTSSON R 
Published: July 2010

SUMMARY
To extend our previous findings that exposure to constant darkness (stimulation of endogenous melatonin release) as well as treatment with exogenous melatonin magnifies the severity of collagen-induced arthritis in mice, we have examined the effects of melatonin cutback by removing the pineal gland. Two strains of mice, DBA/1 and NFR/N, were subjected to surgical pinealectomy. The melalonin levels in sera were reduced by approximately 70% by the pinealectomy compared with the corresponding sham-operated controls. After 3–4 weeks of rest the mice were immunized with rat type II collagen to induce autoimmune arthritis, and the animals were kept in constant darkness during the experiments. In comparison with the controls, all groups of pinealectomized mice showed reduced severity of the arthritis by means of (i) a slower onset of the disease, (ii)a less severe course of the disease (reduced clinical scores), and (iii) reduced serum levels of anti-collagen II antibodies. These effects were not significant in all experiments, but the trends were always the same. Thus, the present results strengthen the hypothesis that high physiological levels of melatonin (which can be induced by exposure to darkness) stimulate the immune system and cause exacerbation of autoimmune collagen II arthritis, while inhibition of melatonin release (pinealectomy or exposure to light) has a beneficial effect.
Adjuvant treatment increases the resistance toMycobacterium aviuminfection of Mycobacteria-susceptible BALB/c mice
Authors: CASTRO A P , ÁGUAS A P , SILVA M T 
Published: July 2010

SUMMARYWe have investigated thc effect of inflammation on host resistance against infection by Mycobacterium avium. an atypical mycobactcria species that is responsible for life-threatening opportunistic infections in AIDS patients. Inflammation was induced in BALB/c mice by two intraperitoneal injections of mineral oil (Freund's incomplete adjuvant, FIA). The BALB/c strain was chosen because it is naturally susceptible to Myco. avium infection. One week after the second FIA injection, the BALB c mice were infected intravenously with 26 ± 106Myco. avium bacilli: at this time, the mice showed systemic granulocytosis because of the FIA injections. The kinetics of the murine infection was determined during 3 months by quantification of Myco. avium loads in the major target organs (liver and spleen) of the mycobacteria. The FIA treatment resulted in a significant decrease in the growth of Myco. avium in the infected BALBx mice. This enhancement in host resistance to Myco. avium infection lasted for 2 3 months. In contrast with BALB/c animals. C3B mice (naturally resistant to Myco. avium infection) did not show an increased anti-Myco. avium action in association with the FIA treatment. The anlimycobaeterial effect of the FIA injections in BALBx mice was compared with that produced by the injection of mycobacterial antigens (heat-killed Myco. tuberculosis) added to the mineral oil (i.e. Freund's complete adjuvant, FCA). The FCA treatment resulted in strong and sustained enhancements in the microbicidal capacities of BALB/c. and also of C3H mice. Data obtained with mutant athymic BALB/c mice revealed that the anti-Myco. avium effect of the FCA treatment was T cell-dependent. Our results indicate that: (i) non-immune inflammatory stimulation (FIA) of Myco. avium-susceptible hosts is able to cause a significant, albeit transient, increase in the resistance to Myco. avium infection; (ii) this protective effect is enhanced if heat-killed mycobacteria arc added to the phlogistic agent (FCA). i.e. if a T cell-dependent response is induced: and (iii) systemic increase in the number of circulating granulocytes may help host defence against Myco. avium infection.