A study of the association of HLA DR, DQ, and complement C4 alleles with systemic lupus erythematosus in Iceland

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To perform an exploratory analysis of the relative contribution of single MHC genes to the pathogenesis of systemic lupus erythematosus (SLE) in a homogenous white population. METHODS: MHC class II alleles and C4 allotypes were determined in 64 SLE patients and in ethnically matched controls. HLA-DR and DQ typing was performed by polymerase chain reaction amplification with sequence specific primers. C4 allotypes were determined by agarose gel electrophoresis. RESULTS: The frequency of C4A*Q0 was significantly higher in patients than in controls (46.9% v 25.3%, p = 0.002). HLA-DRB1, DQA1, and DQB1 alleles in the whole group of SLE patients were not significantly different from those of controls. On the other hand increase in DRB1*03 was observed in the group of patients with C4A*Q0, as compared with patients with other C4A allotypes (p = 0.047). There was no significant correlation between severe and mild disease, as judged by the SLEDAI, and HLADR, DQ alleles and comparing the patients with C4A*Q0 with those with other C4A allotypes there was no significant difference regarding clinical manifestations. CONCLUSION: The results are consistent with the argument that C4A deficiency contributes independently to susceptibility and the pathogenesis of SLE. C4A*Q0 in SLE patients in Iceland shows weaker linkage disequilibrium with DR3 genes than reported in most other white populations and emphasises the role of ethnicity

Naive human T-cells become non-responsive towards anti-TNFalpha (infliximab) treatment in vitro if co-stimulated through CD28

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTumour necrosis factor alpha (TNFalpha) inhibitors are widely used successfully as immunomodulatory agents in various autoimmune diseases. They primarily target the direct pro-inflammatory effect of TNFalpha. They have also been found to be critical for T-cell viability and activation. In this study we evaluated the effect of infliximab treatment under different in vitro stimulatory conditions of naive human cord blood T-cells and adult peripheral blood mononuclear cells (PBMC). PBMC and negatively selected cord blood naive human T-cells were stimulated with alphaCD3 with or without alphaCD28 co-stimulation. The role of in vitro infliximab treatment was evaluated in relation to transforming growth factor-beta1 (TGF-beta1) under the above different stimulatory conditions. Anti-TNFalpha treatment with infliximab significantly suppressed proliferation of adult and cord blood T-cells (P < 0.013) during suboptimal stimulatory conditions. Infliximab prevented division of naive CD4+ and CD8+ T-cells and consequently also activation induced cell death, which was induced after three cell divisions. Interleukin (IL)-2 secretion was significantly decreased during infliximab treatment of suboptimally stimulated T-cells (P < 0.05) while TGF-beta1 levels were unchanged. Strikingly, the anti-proliferative effect of infliximab was overcome by the administration of anti-TGF-beta1 or by the addition of exogenous IL-2. Interestingly, CD28 mediated co-stimulation restored the proliferative response in a dose-responsive manner during infliximab treatment. Finally, exogenous TNFalpha administration during suboptimal stimulation reduced the inhibitory effect of TGF-beta1 upon proliferation (P < 0.03). These results demonstrate that anti-TNFalpha treatment is primarily working upon T cells under low stimulatory conditions and probably through TGF-beta1

The ex vivo induction of human CD103⁺ CD25hi Foxp3⁺ CD4⁺ and CD8⁺ Tregs is IL-2 and TGF-β1 dependent.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.The expression of the integrin αE (CD103), may enhance the retention of regulatory T cells to peripheral inflammatory sites and possibly contribute to their suppressive potential. The aim of this study was to define the regulatory role of IL-2 and TGF-β1 on the CD103 expression and the optimal in vitro conditions for the induction/expansion of human CD4(+) and CD8(+) Tregs. Cord blood mononuclear cells (CBMC) were stimulated under various culture conditions, including anti-CD3, anti-CD28, IL-2 and TGF-β1. TGF-β1 and IL-2 were both required for optimal expression of CD103. In addition, TGF-β1 and IL-2 synergistically induced CD103 expression on CD8(+) T cells, whereas, only additive induced expression was noted on CD4(+) T cells. Surprisingly, CD103 expression was not dependent upon CD28 costimulation. IL-2 also played a central role in CD103 expression by CD25(hi) Foxp3+ Tregs. IL-2, TGF-β1 and anti-CD3 defined the optimal stimulatory conditions favouring the induction/expansion of both CD4(+) and CD8(+) human Tregs from naive CBMC. Thus, this study provides new insights into the regulatory role of IL-2 upon CD103 expression by human cord blood CD4(+) and CD8(+) T cells. Furthermore, it identifies the in vitro culture conditions driving the differentiation of the novel phenotype CD4(+) and CD8(+) CD103(+) CD25(hi) Foxp3+ Tregs from human CBMC.Landspitali University Hospital Research Fund, University of Iceland Research Fun

Evidence for extrathymic T cell maturation after thymectomy in infancy

Our previous study showed that children who had been partially or completely thymectomized during heart surgery as infants had lower proportions and numbers of total lymphocytes and reduced proportions of T cells (CD3(+)), helper T cells (CD4(+)) and naive T cells (CD3(+) CD4(+) CD45RA(+)), but normal proportion of cytotoxic T cells (CD8(+)). In this study T lymphocytes from a selected group of eight of these children and age- and gender-matched controls were characterized further using flow cytometry to determine phenotypes of T cells and T cell subsets related to T cell regulation and phenotypes suggestive of extrathymic maturation. Immune function was assessed by measuring autoantibodies and antibodies against vaccines. The study group had significantly lower numbers of all the main subsets of T lymphocytes and the composition was different. Thus, the proportions of lymphocytes with the following phenotypes: CD3(+), CD2(+), CD7(+), CD4(+), CD62L(+), CD4(+) CD62L(+) and CD4(+) CD69(−) were significantly reduced in the study group compared with the control group, but significantly higher proportions were seen of lymphocytes expressing CD8α(+) CD8β(−) and TCRγδ(+) CD8α(+) CD8β(−). The absolute number and proportion of CD4(+) CD25(+) cells were reduced but the proportions of the subgroup of naive regulatory T cells (CD4(+) CD25(+) CD62L(+)) and non-activated regulatory T cells (CD4(+) CD25(+) CD69(−)) were not reduced in the thymectomized children. We conclude that the phenotypic characteristics of T lymphocytes of children who have lost their thymus in infancy are indicative of extrathymic maturation. T regulatory cells appear to be less affected than other subsets by the general reduction in T cell numbers

International Whores Day rally participants congregating on the Sydney Opera House steps, 2007 [picture] /

Title devised by cataloguer based on information supplied by vendor.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn3997297; Purchased from the photographer, 2007. Sydney sex workers rally on the Opera House steps to celebrate International Whore's Day, (2 June). In 1975 sex workers staged a sit-in at a church in Lyon, France. This protest was to draw attention to a wide range of issues, including Police harassment and Government legislation. Sex workers in France were repeatedly jailed, fined and taxed under the existing laws. This sit-in marked the beginning of International Whore's Day and is now celebrated in many countries around the world on 2 June

The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life

Infants undergoing open heart surgery often have all or part of their thymus removed. The activity of the immune system has not been investigated thoroughly in these children, and only shortly after the operation. Therefore, it was decided to investigate the activity of the immune system in more detail in children several years after their operation. Peripheral blood samples from 19 children who had undergone open heart surgery during their first months of life was collected (study group) and from 19 age- and gender-matched children (control group). The activity of the immune system was evaluated by measuring the number of different cell types in peripheral blood, the phenotype of lymphocytes and the response of T cells following in vitro stimulation by mitogen, tetanus toxoid and measles antigen. The study group had significantly lower counts of total lymphocytes, which was reflected in a lower number of T cells but not B cells. Furthermore, the study group had significantly lower proportion of T cells (CD3(+)) and helper T cells (CD4(+)), but not cytotoxic T cells (CD8(+)). The level of neutrophils in peripheral blood was significantly higher in the study group. This may indicate enhanced innate immunity when the acquired immunity is defective. The results indicate a shift to extrathymic T cell maturation, which is less efficient for CD4(+) helper cells than for CD8(+) cytotoxic cells

The association between coeliac disease, dermatitis herpetiformis and certain HLA-antigens in Icelanders

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldTwenty-eight cases of coeliac disease (CD) and seven of dermatitis herpetiformis (DH) have been verified in Iceland. Standard serological techniques were used for HLA typing. Twenty-five individuals with CD were typed, 21 (84%) of whom carried DR3,DQ2. Twelve of these 25 (48%) had DR3,DR7, DQ2, which makes them possibly homozygous for DQ2, and suggests that homozygosity of DQ2 increases the risk for CD. The four DH patients that were typed all had HLA-B8,DR3,DQ2. It is concluded that CD and DH are associated with DR3, DQZ in Icelanders