bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage of IgA deficiency to Gm allotypes; the influence of Gm allotypes on IgA-IgG subclass deficiency
Authors: Oxelius V-A , Carlsson A-M , HammarstrÖM L , BjÖRkander J , Hanson L Å 
Published: July 2010

SUMMARYIgA deficiency (IgAD) is the most common immunodeficiency, characterized by an arrest in B cell differentiation. It has a sporadic occurrence or variable inheritance pattern, and is also linked to the HLA genes. IgA deficiency is sometimes associated with IgG subclass deficiency. In this study the Gm allotypes, as genetic characteristics of the IgG1, IgG2 and IgG3, were analysed in 83 Caucasian IgAD individuals. Half of the patients presented with IgG4 &lt; 0·01 g/l compared with 5% (P &lt; 0·001) in a healthy population. Three of the 83 had significantly low IgG2 and four had significantly low IgG3 levels. Gm allotype frequencies in IgAD deviated compared with a normal population. Of the 83 patients, 44 (53%) showed homozygous G2m(“,”) expression on the IgG2 locus (33% in controls, P &lt; 0·01). In IgAD the Gm(a, g) haplotype was more frequent (43%) compared with controls (31%, P &lt; 0·01). The Gm homozygous phenotype Gm(a', g/a', g) was most common, found in 20 of 83 patients (24%, P &lt; 0·05) compared with controls (14%). On the other hand the Gm(f,n,b) haplotype of IgAD was rare (28%) compared with controls (45%, P &lt; 0·001). The low IgG4, &lt; 0·01 g/l, found in 50% of the patients, was even more frequent (56–69%) among the G2m(“,”) phenotypes. IgG subclass levels were given for different Gm phenotypes of the IgAD group and compared with controls. Significantly low IgG4 was revealed in the Gm(a,“,g/a,”,g) phenotype (P &lt; 0·01) and significantly low IgG2 in the Gm(a,“,g/f,”,b) phenotype (P &lt; 0·01). The Gm(a,“,g/f,”,b) phenotype contained the three patients found with IgG2 levels &lt; - 2 s.d., and the four patients with IgG3 levels &lt; -2 s.d. were present among those with the homozygous Gm(a,“,g/a,”,g) phenotype; both phenotypes with G2m(“,”) on the IgG2 locus. The ‘compensatory’ increase of IgG was significant for both IgG1 and IgG3 in all Gm phenotypes, but in the Gm(a,“,g/f,”,b). Thus, the susceptibility of IgAD with the additional IgG antibody deficiencies, down-regulated IgG4 and IgG2/IgG3, is associated with Gm allotypes, especially the homozygous G2m(“,”) expression on the IgG2 locus.
Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE)
Authors: Suzuki T , Suzuki N , Engleman E G , Mizushima Y , Sakane T 
Published: July 2010

SUMMARYThe principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.
Regulatory effects of IL-13 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis
Authors: Hart P H , Ahern M J , Smith M D , Finlay-Jones J J 
Published: July 2010

SUMMARYActivated macrophages are central to the destructive processes of chronic inflammatory arthritis. In this study, it was hypothesized that IL-13, a product predominantly of'Th2-type’ lymphocytes, may be used therapeutically to down-regulate monocyte/macrophage activities at sites of chronic inflammation. Synovial fluid mononuclear cells were isolated from 12 patients with chronic inflammatory arthritis. Peripheral blood mononuclear cells (PBMC) were isolated at the same time as synovial fluid cells from all 12 patients, IL-13 significantly inhibited lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-α) production by mononuclear cells from peripheral blood, but not synovial fluid. In contrast, IL-13 inhibited LPS-induced IL-1β production by all cells, and as a positive response to IL-13, CD23 expression was increased on both cell populations. Blood monocytes cultured for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) or M-CSF responded to IL-13 in a manner similar to that detected for synovial fluid-derived cells, with suppression of LPS-induced IL-1β, but not TNF-α, production. In all experiments, the responses to IL-13 were very similar to those detected to IL-4, but differed from those measured with IL-10. Thus, the responses to IL-13 by synovial fluid cells and cultured monocytes are not equal to those of blood monocytes. The similar responses to IL-4 and IL-13 support claims of a common element for signalling from the IL-4 and IL-13 receptors. Furthermore, the activity of a common receptor chain may be altered by monocyte activation and differentiation.
IL-1β and IL-6 stimulate the production of platelet-activating factor (PAF) cultured rabbit synovial cells
Authors: Gutierrez S , Palacios I , Egido J , Zarco P , Miguelez R , GonzÁLez E , Herrero-Beaumont G 
Published: July 2010

SUMMARYThe aim of this study was to determine whether synovial cells are capable of producing PAF in the presence of cytokines such as IL-1βand IL-6 and other stimuli. Synovial cells were obtained from joints of healthy rabbits. PAF production was assayed by measurement of serotonin release in rabbit platelets and the incorporation of 3H-acetate into PAF. Synovial cells produced PAF after 5 min of incubation with ionophore A23187, reaching the maximal amount at 15 min (4·3 ± 0·7 ± 10−3 pmo1 of PAF/mg protein, P &lt; 0·005, n= 4), and declining afterwards. The treatment of synoviocytes with IL-1β and IL-6 induced synthesis of PAF after 5 min of stimulation, reaching the greatest production at 15 min with IL-6 and 30 min with IL-1β (3·6 ± 1·1 ± 10−3 and 3·3 ± 1·2 pmol of PAF/mg protein, respectively, P &lt; 0·05, n= 4). The incubation of the cells with PMSF, an inhibitor of acetylhydrolase, before the addition of the stimuli, increased the incorporation rate of 3H-acetate, suggesting a rapid degradation of PAF by synoviocytes. These results demonstrate that synovial cells can produce PAF after stimulation with agonists, such as ionophore, and cytokines. Thus, PAF, acting alone or with other mediators, could amplify the inflammatory joint reaction.
Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease
Authors: Yamazaki K , Nakajima T , Hara K 
Published: July 2010

SUMMARYIL-2, interferon-gamma (IFN-γ), IL-4 and IL-6 producing T cells in periodontitis and gingivitis-affected human tissues were investigated by immunohistochemistry to clarify the relationship between T cell functional subsets and disease entity. Using alkaline-phosphatase anti-alkaline-phosphatase technique, the relative proportions of each cytokine-producing T cell were calculated in the crevicular 1/3, middle 1/3 and oral 1/3 areas selected in the connective tissue of sections. CD19:CD3 and CD4:CD8 ratios were determined on the serial sections. Compared with gingivitis tissues, the proportion of cytokine-producing cells in periodontitis-affected samples was higher overall in the crevicular 1/3 (P &lt; 0·02). The middle 1/3 exhibited a higher percentage of cytokine-producing cells, except for IL-6-producing cells. Frequencies of cytokine-producing cells in the oral 1/3 did not differ. IL-4 was the prominent cytokine in periodontitis-affected tissues, with the highest proportion detected in the crevicular 1/3. The CD19:CD3 ratio was higher in periodontitis tissues irrespective of the location, indicating a B cell dominance in periodontitis lesions. Furthermore, a significant positive correlation between the proportion of IL-4-producing cells and the CD19:CD3 ratio was noted. The CD4:CD8 ratio consistently exceeded 2·0 in both periodontitis and gingivitis. These results suggest that immunoregulation of both periodontitis and gingivitis are T cell-dependent, but in periodontitis type 2 helper T cells predominate and thereby control B cell activation.
Recognition of a unique peptide epitope of the mycobacterial and human heat shock protein 65–60 antigen by T cells of patients with recurrent oral ulcers
Authors: Hasan A , Childerstone A , Pervin K , Shinnick T , Mizushima Y , Van Der Zee R , Vaughan R , Lehner T 
Published: July 2010

SUMMARYT cell epitopes of the 65-kD heat shock protein (hsp) were investigated in patients with recurrent oral ulcers (ROU). Peripheral blood mononuclear cells were stimulated with overlapping synthetic peptide (15ers), derived from the sequence of the 65-kD hsp of Mycobacterium tuberculosis. Specific lymphoproliferative responses were stimulated only with peptide 91–105 in ROU, compared with healthy or disease controls (P &lt; 0·01). This was confirmed by studying 760 short term cell lines generated with the 65-kD hsp and then stimulated with the peptides. The frequency of short term cells lines responding to peptide 91–105 in ROU was significantly greater than in healthy (P &lt; 0.0001) or disease controls (P &lt; 0·01). A comparative investigation with the homologous human 60-kD hsp peptide 116–130 also showed significantly greater lymphoproliferative responses in ROU than in healthy (P &lt; 0·01) or disease controls (P &lt; 0·001). The potential involvement of the T cell epitope 91–105 in the pathogenesis of ROU is supported by finding a significant increase in the lymphoproliferative responses stimulated with peptide 91–105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P &lt; 0·05). The results suggest that oral ulceration might be initiated by the microbial hsp peptide 91–105 stimulating the mucosal Langerhans cells, which may generate autoreactive T cell clones primed to the homologous peptide 116–130.
Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens
Authors: Baca-Estrada M E , Wong D K H , Croitoru K 
Published: July 2010

SUMMARYIn Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A)-stimulated peripheral blood mononuclear cells (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of Vβ8 T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8+ T cells expressing Vβ8. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of Vβ8 and Vβ12 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the Vβ12 subset, SEE stimulation failed to increase cytolytic activity of Vβ8+ T cells in spite of the expansion of Vβ8+ T cells. These results suggest that the changes in cytotoxic function observed in Vβ8 T cells in Crohn's patients may reflect previous exposure to a Vβ8-selective superantigen.
Antibodies to theCryptococcus neoformanscapsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV− individuals
Authors: Deshaw M , Pirofski L-A 
Published: July 2010

SUMMARYMurine MoAbs to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) polysaccharide are protective in mice in vivo and in vitro. The prevalence of protective anti-GXM antibodies in human serum is unknown. To provide further insight into the human antibody response to C. neoformans we determined the prevalence, isotype, and IgG subclass utilization of human anti-GXM antibodies in HIV+ and HIV− sera by a sensitive antigen capture ELISA assay. One hundred and twenty-three sera from the Bronx Municipal Hospital Centre serum bank were studied retrospectively. Seventy were from HIV+ individuals, 10 with a history of cryptococcal meningitis (CM), and 53 were from HIV− individuals. Serum GXM determinations were also performed on 61 HIV+ sera. Our results demonstrated that anti-GXM IgG, IgA, and IgM are ubiquitous in both HIV+ (including those with CM), and HIV− sera. Anti-GXM IgA titres and total serum IgA concentration were elevated in HIV+ sera. Anti-GXM IgG antibodies were almost exclusively isotype-restricted to the IgG2 subclass. Our data also demonstrated elevations of anti-bovine serum albumin (BSA) titres in HIV+ sera. Taken together, our findings confirm hypergammaglobulinaemia and expansion of anti-protein (BSA) antibodies in HIV+ individuals and isotype restriction of human anti-carbohydrate (GXM) antibodies to the IgG2 subclass. Our report of ubiquitous anti-GXM antibodies of the IgG and IgA isotypes suggests that anti-GXM antibodies exist before HIV infection.
Anti-inflammatory activity of salmeterol: down-regulation of cytokine production
Authors: Sekut L , Champion B R , Page K , Jr J A MENIUS , Connolly K M 
Published: July 2010

SUMMARYElevation of intracellular cAMP levels has been shown previously to inhibit cytokine secretion by various cell types in vitro. Since salmeterol is a β2-agonist which activates adenylate cyclase, its ability to inhibit cytokine production was evaluated. Though salmeterol, and the related drug albuterol, did not inhibit IL-1β production in vitro, both drugs did inhibit tumour necrosis factor-alpha (TNF-α) secretion by lipopolysaccharide (LPS)-activated THP-1 cells with similar IC50S of approximately 0·1μm. This inhibition was effectively reversed by the β2-antagonist oxprenolol, indicating that the inhibition was mediated through the β2-adrenergic receptor. A strikingly different reactivity profile was seen with T cells. Salmeterol was able to inhibit the activation of both mouse and human T cells, as measured by proliferation and IL-2 secretion in response to anti-CD3 antibody, whereas albuterol was completely inactive in these assays. This T cell inhibition by salmeterol was about 10-fold less potent than that for TNF-α production, and was not reversed by a β2-antagonist, indicating that a different mechanism was involved in the effect of salmeterol on T cells. Paralleling the TNF-a inhibitory activity in vitro, oral dosing of salmeterol and albuterol inhibited LPS-induced increase in murine serum TNF level in vivo, with ED50s of approximately 0·1 mg/kg. This inhibition could be abrogated by dosing orally with the β-blocker propranolol. The long-acting pharmacological profile of salmeterol was apparent in that it maintained its efficacy for 3h, while albuterol had a much shorter duration of action. Salmeterol also had some protective effects in the galactosamine/LPS model of endotoxic shock, which is dependent upon TNF-α production. Though salmeterol inhibited serum TNF-α levels by up to 94% in this assay, it protected less than 50% of the animals from the lethal effects of the LPS/galactosamine mixture. This observation suggests that functional levels of TNF-α localized in tissues may not be accurately reflected by serum levels.
Co-Stimulation of T cells via CD28 inhibits human IgE production; reversal by Pertussis toxin
Authors: Van Der Pouw-Kraan C T M , Rensink H J A M , Rappuoli R , Aarden L A 
Published: July 2010

SUMMARYIn lymphocyte cultures, IgE production was achieved by stimulating T cells with anti-CD2 and IL-2. Here we show that anti-CD28, in the presence or absence of IL-2, reduces this IgE production approximately 10-fold. This inhibition of IgE production was almost completely reversed by Pertussis toxin (PT). PT had no effect on IgE production when the cells were stimulated in the absence of anti-CD28. No major effects of PT were found on IgM production. PT had no effect on purified B cells, stimulated with IL-4 and anti-CD40. In the presence of saturating amounts of rIL-4 similar results were obtained, albeit the absolute amounts of IgE produced were higher in all situations. Furthermore, PT-induced IgE production was still dependent on IL-4, as was evident from experiments in which anti-IL-4 was added to the culture. The IgE enhancing effect was dependent on the adenosine diphosphate (ADP)-ribosyltransferase activity of PT, because a mutant molecule lacking this activity was not able to restore anti-CD28-induced inhibition of IgE synthesis. Thus, we show that co-stimulation with anti-CD28 causes an inhibition of T cell-dependent IgE production by B cells, which inhibition can be specifically overcome by PT. An analysis of the molecular pathways underlying this phenomenon may contribute to our understanding of the regulation of IgE synthesis in (patho)physiological conditions.
Animal models in ANCA-vasculitis
Authors: Kettritz R , Yang Jia Jin , Kinjoh K , Jennette J C , Falk R J 
Published: July 2010

SummaryThe animal models described to date suggest pathogenicity of ANCA. Unfortunately, none of the models unequivocally proves that ANCA are pathogenic. Further search for a suitable animal model to document or exclude causal significance of ANCA in vasculitis is needed.
Expression of IL-10, IL-4 and interferon-gamma in unstimulated and mitogen-stimulated peripheral blood lymphocytes from HIV-seropositive patients
Authors: Diaz-Mitoma F , Kumar A , Karimi S , Kryworuchko M , Daftarian M P , Creery W D , Filion L G , Cameron W 
Published: July 2010

SUMMARYInfection of immune cells with HIV induces dysregulation of cytokines which may play a vital role in HIV pathogenesis. We analysed the expression of T helper type I (Th1) (interferon-gamma (IFN-γ)) and Th2 (IL-4, IL-10) type cytokines in peripheral blood lymphocytes (PBL) from HIV patients. The semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that IFN-γ mRNA in unstimulated PBL was significantly decreased and IL-10 mRNA was significantly upregulated in patients with &lt; 400 CD4+ T cells/mm3 (n= 30) as compared to patients with &gt; 400 CD4+ T cells/mm3 (n= 6) and normal controls (n= 16). In addition. IL-10 mRNA levels were inversely associated with IFN-γ expression. Similar results were obtained by measuring IL-10 production in the supernatants of PBL cultured in vitro without stimulation by employing an enzyme immunosorbent assay (ELISA). However, the levels of IL-4 and IFN-7 produced by unstimulated PBL were undetectable by ELISA. Mitogen stimulation of PBL revealed two groups of HIV individuals based on IL-10 production. PBL from one set of individuals produced low levels of IL-10 (low IL-10 producers) whereas the other group produced IL-10 comparable lo that of normal controls (IL-10 producers). Production of IL-4 was significantly reduced in HIV+ individuals with&lt;400 CD4+ T cells/mm3 as compared to the normal controls. However, ability to produce IFN-γ by mitogen-stimulated total PBL and CD4+ purified cells was not impaired in HIV+ individuals. These results suggest that unstimulaied and mitogen-stimulated PBL of HIV+ individuals exhibit dysregulation of Th2 type cytokines which may play a role in HIV immunopathogenesis.
Demonstration of virus-specific CD8+ memory T cells in measles-seropositive individuals by in vitro peptide stimulation
Authors: Nanan R , Carstens C , Kreth H W 
Published: July 2010

SUMMARYCD8+ cytotoxic T lymphocytes (CTL) in measles virus infection have been difficult to investigate due to the strong immunosuppressive effects exhibited by infectious measles virus in vitro. In order to circumvent immunosuppression we used predicted peptide epitopes to induce measles virus-specific CTL, This was done by screening the structural proteins of measles virus for HLA-A2.1 peptide-binding motifs with valine in position 2 and leucine in position 9. Synthetic peptides np210 218. np226-234, and np340-348 from the nucleoprotein, peptide hp29-37 from the haemagglutinin protein, and peptide pp 519-527 from the polymerase protein were synthesized and used to expand measles virus-specific CD8+ CTL in vitro. Induction of CTL with synthetic peptides was restricted to HLA-A2-positive peripheral blood mononuclear cells (PBMC) from measles-seropositive individuals. We conclude that this method is a useful tool to demonstrate memory CD8+ CTL in measles-seropositive adults and to evaluate the role of structural proteins in CTL responses against measles.
T cell clones from a non-leprosy exposed subject recognize theMycobacterium leprae18-kD protein
Authors: Adams E , Basten A , Prestidge R , Britton W J 
Published: July 2010

SUMMARYAlthough Mycobacterium leprae shares many protein antigens with other mycobacterial species, there is a degree of specificity in the T cell response to the organism. This is evident in the failure of cross-protection between mycobacterial species and the specific unresponsiveness to M. leprae in lepromatous leprosy patients. The antigenic basis of this specificity is unresolved, but the M. leprae 18-kD protein is one candidate because of its restricted distribution and the isolation of M. leprae-specific T cell clones reactive with the protein from M. leprae-vaccinated subjects. In the course of analysing the human T cell repertoire to mycobacteria we have isolated further CD4+ T cell clones reactive with this protein from a subject who had never been exposed to M. leprae. These clones did not respond to other mycobacteria, including M. tuberculosis and M. bovis (BCG). In addition, they were unreactive with the M. tuberculosis 16-kD protein which has recently been shown to have limited amino acid identity with the M. leprae 18-kD protein. Both clones reacted with peptide 38 50 from the M. leprae 18-kD protein, the T cell response to which a restricted by HLA-DR4. Although homologues for the gene encoding the M. leprae 18-kD antigen have been identified in M. avium and M. intracellulare, the clones failed to respond to preparations of M. avium. Both clones secreted interferon-gamma (IFN-γ) and tumour necrosis factor-beta (TNF-β) and were cytolytic against autologous targets pulsed with peptide 38-50 or the 18-kD protein. The nature of the antigen which stimulates this apparently “M. leprae-specific” response is unknown. Nevertheless the recognition of the 18-kD protein by individuals not exposed to leprosy indicates that this protein may not be suitable as a reagent to distinguish between infection with M. leprae and other pathogenic mycobacteria.