This article portrays the findings of research on the experiences of inclusion/exclusion of people with disabilities in faith communities. This journey was undertaken with a group of people with ...disabilities in Pietermaritzburg, South Africa, during 2009 and 2010. In narrations of the journey, participants expressed their experiences of exclusion, of not being considered, and of their personhood not always respected in faith communities. However, the journey also revealed suggestions to how their inclusion can be enhanced by changing practices, developing understanding of the needs of people with disabilities, and raising awareness. The article will conclude with recommendations for ways that people with disabilities and others in faith communities can journey together in faith communities to the benefit of all.
Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains in vivo produced cytokines and inflammatory mediators, including a factor that induces IgG2b production of lipopolysaccharide ...(LPS) preactivated murine B lymphocytes. In order to determine the mechanism by which RA-SF acts on LPS activated mouse B cells, CBA/N mice were used as an experimental model. The X-linked immunodeficiency of these mice is caused by a point mutation in the Bruton's tyrosine kinase (btk) gene. We have earlier shown that RA-SF can reconstitute the CBA/N B cell deficiency in vitro and in vivo, with regard to IgG2b production after LPS stimulation. Since transforming growth factor (TGF)-beta has been suggested to be a switch factor for IgG2b, we aimed at investigating the role of TGF-beta in our experimental system. We found that TGF-beta could not mimic the effect of RA-SF on CBA spleen cells. A small increase of IgG2b secretion was observed with spleen cells from normal CBA mice, whereas Ig secretion of all isotypes was suppressed in CBA/N spleen cells treated with TGF-beta at any concentration. Neutralizing antibodies against TGF-beta suppressed the response of CBA B cells, whereas the response by CBA/N B cells was enhanced by the same antibody preparation. Here we also show that the abnormal B cell responsiveness to TGF-beta, typical of CBA/N, co-segregates with the btk mutation in male (CBA x CBA/N)F2 spleen cells. This was determined by allele specific PCR recognizing the identified base substitutions of the btk gene, typical of the two strains. We propose that RA-SF contains a factor, separate from TGF-beta, that is involved in the differentiation of IgG2b expressing cells.
In tissue culture, immune lymph node cells containing foreign his-tocompatibility antigens of the H-2 type exert marked cytotoxic effects on tumor cells incompatible with the H-2 antigen. An equally ...pronounced effect is obtained when normal allogeneic and semi-isologous lymphoid cells of F$_{1}$ hybrids are caused to aggregate around the target tumor cells by treating the cultures with either heat-inactivated rabbit antiserum to mouse cells or phytohemagglutinin. Isologous lymph node cells have no effect. Thus, aggregation of lymphoid cells and target cells is a necessary but insufficient requirement for cytotoxicity in vitro; in addition, close contact must be established between histoincompatible cells.
: Background: Xenotransplanted patients produce xenospecific IgG1 antibodies directed against epitopes other than Galα1,3Gal. IgG1 antibody production is believed to be dependent upon T cell help. ...Therefore, as a natural continuation of our work aimed at characterizing the xenoimmune antibody response against pig islet cells, we have also examined the T cell response. T cell reactivity against islet cells is believed to result from indirect antigen presentation, and our in vitro study was designed to mimic the response in vivo. The main purpose of this study was to characterize the phenotype, the immunological specificity and the functional capacity of indirectly activated T cell clones, reactive against pig islet cell antigens.
Materials and methods: Human T cell clones, activated against pig islet cells in the presence of autologous antigen‐presenting cells, were produced from limiting dilutions of bulk cultures. Clonality was investigated by T cell receptor Vβ (TcRVβ) expression analysis. Clonal specificity was studied in proliferation assays using different pig cells as stimulators. ELISpot experiments were performed to detect cytokine production patterns. The cytotoxic capacity of the clones was assessed using standard cell‐mediated lysis tests and different porcine and human target cells. Several long‐term bulk cultures of human lymphocytes, indirectly activated against pig islet cells, maintained for up to 60 days, were used as a control for possible bias in the selection of the clones.
Results: Nineteen CD4+ TcRVαβ+ T cell clones were recovered. No activation of natural killer T cells or γδ‐T cells was recorded. There was no bias in the TcRVβ‐usage. The immunological specificity differed between clones; some were specifically reactive against pig islet cell antigens, while others were reactive with antigens present on a variety of pig cells. All clones produced a broad spectrum of cytokines, e.g. interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, interleukin (IL)5, IL10 and IL13, with no evidence of bias for a particular phenotype. None of the T cell clones were cytotoxic against pig islet cells, but two clones were cytotoxic against pig phytohemagglutinin (PHA)‐blasts.
Conclusion: The analysis of several, indirectly activated, human CD4+ T cell clones shows that the response against pig islet cells is heterogeneous both with regard to immunological specificity and functional characteristics. This heterogeneity was further confirmed by analysis of the long‐term bulk cultures of human lymphocytes, indirectly activated against pig islet cells.
It is well established that in susceptible mouse strains, chronic treatment with subtoxic doses of mercuric chloride (HgCl2) induces a systemic autoimmune disease, which is characterized by increased ...serum levels of IgG1 and IgE antibodies, by the production of anti-nucleolar antibodies and by the development of immune complex-mediated glomerulonephritis. Susceptibility to mercury is partly under the control of major histocompatibility complex genes. To study the susceptibility to mercury further, we investigated the in vivo effects of mercury in young autoimmune disease prone (NZB x NZW)F1 (H-2d/z) mice prior to establishment of spontaneous autoimmune disease. Mercury-susceptible SJL (H-2s) mice and mercury low-responder BALB/c (H-2d) mice were used as positive and negative controls, respectively. In (NZB x NZW)F1 mice, treatment with mercury stimulated an intense antibody formation characterized by increased numbers of splenic IgG1 and IgG3 antibody-producing cells as well as by elevated serum IgE levels. Injection with mercury also induced an increased production of IgG1, IgG2b and IgE antibodies in SJL, but not in BALB/c mice. The mercury-induced IgG1 response in (NZB x NZW)F1 and SJL mice was found to be polyclonal and autoantibodies against double-stranded (ds)DNA, IgG, collagen, cardiolipin, phosphatidylethanolamine as well as antibodies against the hapten trinitrophenol were produced. In addition, SJL, but not (NZB x NZW)F1 or BALB/c mice, produced IgG1 anti-nucleolar antibodies after treatment with mercury. Further studies demonstrated that (NZB x NZW)F1 and SJL mice developed high titers of renal mesangial immune complex deposits containing IgG1 antibodies 3 weeks after injection with mercury. Thus, a mouse strain genetically prone to develop spontaneous autoimmune diseases is highly susceptible to mercury-induced immunopathological alterations.
Monocytes are suggested to harbor latent cytomegalovirus (CMV) in peripheral blood, which concurs with the finding that all CMV-susceptible cells carry the CD13 surface molecule. Here, we ...investigated whether all latently and productively CMV-infected peripheral blood mononuclear cells (PBMCs) could be eliminated by depletion of CD13-expressing cells.
Depletion of CD13-positive cells was performed with monoclonal antibodies and magnetic cell separation (MACS) beads followed by MACS. CMV DNA and cDNA were amplified by polymerase chain reaction with specific primers for two CMV genes, major immediate early and phosphoprotein 150. The presence of infectious virus was tested by incubating homogenized in vitro- or in vivo-infected PBMCs with human fibroblasts. CMV infection of fibroblasts was detected by intracellular expression of CMV proteins.
Elimination of CD13-positive PBMCs removed productively in vitro- and in vivo-infected cells, as demonstrated by detection of infectious virus only in PBMC fractions containing CD13-positive cells. In support of this finding, CMV RNA was not detected in pure CD13-negative cell fractions. Furthermore, CMV DNA was found exclusively in CD13-positive PBMCs obtained from patients with acute CMV infection.
Our data suggest that CMV replicates exclusively in CD13-positive PBMCs. These findings have important clinical applications, because the elimination of CD13-positive cells may reduce the risk for transmission of latent CMV in blood products and bone marrow grafts and thereby also decrease the risk for CMV-induced complications, such as chronic graft-versus-host disease in bone marrow transplant patients.
Cytomegalovirus (CMV) infection has been suggested to be associated with certain autoimmune phenomena as well as with the development of chronic graft-versus-host disease (cGVHD) following allogeneic ...bone marrow transplantation. Earlier we found that the CMV-associated host protein CD13 is immunogenic during CMV infection in allogeneic bone marrow transplant patients, resulting in production of CD13-specific antibodies. Here we found a close correlation between CD13-specific immunity and later development of cGVHD in 26 of 33 patients who could be evaluated for this disease. Of seven patients with CMV disease, six developed extensive cGVHD, all of whom had CD13 specific antibodies (P=0.0002). All 14 patients who were CD13-immune later developed either limited or extensive cGVHD (P=0.0008). Antibodies in sera from the CD13-immune patients suffering from cGVHD recognized normal structures in cryosectioned skin biopsies from control individuals, producing a staining pattern similar to that of CD13-specific monoclonal antibodies. The antibody binding could be specifically blocked by preincubation of the skin sections with a mixture of monoclonal antibodies against CD13, and was also abolished after preabsorption of sera to mouse cells expressing human CD13. No other common autoantibodies were identified in more than single patients. Furthermore, in vivo binding of IgM antibodies in a CD13-like fashion was preferentially demonstrated in skin and oral mucosa biopsies from the CD13-immune patients suffering from cGVHD. Thus, we suggest that CMV-induced CD13-specific autoimmunity contribute to tissue damage in chronic graft-versus-host reactions.
An adequate method that will permit rapid specificity determination of donor-reactive antibodies is urgently needed. Such a method could also be used for monitoring the presence of HLA antibodies in ...panel screening. We here describe a method using magnetic beads coated with soluble HLA antigens that can be directly added to patient serum for efficient absorption of HLA antibodies. The entire procedure takes 45 min, and can therefore be easily adopted for use in acute crossmatching situations. Furthermore, since no live cells are required for identification of alloantibodies in the screening for HLA specific panel-reactive antibodies, it can be used as an ideal complement for screening of panel-reactive antibodies. Binding of antibodies to the antigen-coated beads is easily visualized using flow cytometry. A new method for quick purification of soluble HLA antigens from a pool of lymphocytes or thrombocytes is also presented.
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