Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The exact role of B cells in antigen presentation to naive T cells in vivo is presently not known. Here, we demonstrate the ability of a B cell subset consisting of B7-2pos-B cells to prime autoreactive T cells in B cell-deficient mice. In contrast, B cell-deficient mice are unable to mount a similar initiation and expansion of the autoimmune response. The expression of the B7-2 costimulatory molecule as well as the specificity to a self-antigen, either murine cytochrome c or murine ribonucleoproteins (the target of autoimmunity in SLE), enabled B cells as antigen-presenting cells to induce naive lymph node T cells to proliferate and to express IFN-gamma, IL-4, IL-5, and IL-10 cytokine mRNAs. In contrast, neither adoptively transferred B7-2neg-B cells nor nonspecific B7-2pos-B cells were able to activate naive T cells. In addition, anti-B7-2 treatment prevented the in vivo expression of the IL-4, IL-5, and IFN-gamma cytokine mRNA responses. Our results suggest a major role of autoantigen-specific B7-2pos-B cells in breaking T cell tolerance to self-antigen.
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PMID:B lymphocytes as autoantigen-presenting cells in the amplification of autoimmunity. 918 42

The objective of the this study was to determine the cytokine profile of aging mice and to establish whether changes in cytokine production account for the fact that aging mice develop a milder disease than the young in response to induced experimental systemic lupus erythematosus (SLE). Cytokine secretion was evaluated in groups of BALB/c and C3H.SW mice at different ages between 2 and 24 months. The production of IL-2, IL-4, IL-10, IFN gamma and TNF alpha was determined in supernatants of ConA-stimulated splenocytes and that of IL-1 in the supernatants of LPS-stimulated peritoneal macrophages. A gradual age-related decline was observed in the production of IL-2 and IFN gamma, whereas the levels of IL-4, IL-10, IL-1 and TNF alpha progressively increased with aging, in unimmunized BALB/c and C3H.SW mice. Experimental SLE was induced in 2 and 10 month old C3H.SW mice by immunization with the monoclonal anti-DNA antibody bearing the 16/6 Id. The characteristic cytokine profile following immunization of 2 month old mice was early increased production of TNF alpha and IL-1, followed by a peak of Th1 type cytokines (IL-2, IFN gamma). At a later stage of the disease, a peak of Th2 type cytokines (IL-4, IL-10) was observed that was concomitant with low levels of Th1 cytokines. In contrast, in the 10 month old mice that were immunized with 16/6 Id only a mild increase in all the above cytokines was observed. We suggest that the lower autoantibody production and moderate clinical manifestations in aging mice with experimental SLE are causally related to the decreased production of pro-inflammatory cytokines at the initial stages of the disease followed by a lower production of both Th1 and Th2 type cytokines.
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PMID:Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus afflicted mice. 922 10

We describe a patient presenting with systemic lupus erythematosus (SLE) and concomitant low-grade (Ig) non-Hodgkin's lymphoma of the B cell type (B-NHL). Although the association of autoimmune disorder and lymphoma is well conceived, there is only scarce information available as to the simultaneous occurrence of both disease conditions in one patient. As in this patient diagnosis of Ig B-NHL was also based on the detection of a monoclonal population of CD5+ B lymphocytes, and given that the polyclonal expansion of CD5+ B cells has been previously reported in rheumatoid arthritis (RA), Sjogren's syndrome (SS) and single cases of SLE, the observations we made in this patient led us to discuss the role of the CD5+ population in the development of rheumatic disorders and concomitant lymphoid malignancy. Moreover, since impaired production rates of interleukin 3 (IL-3) and interleukin 4 (IL-4) have been associated with an abnormal expansion of CD5, lymphoma cells and seeing that soluble interleukin 2 receptor (sIL-2R) serum levels were found to be positively correlated with disease activity both in SLE and Ig B-NHL, these parameters were investigated and related to the patient's disease state throughout the entire clinical observation period.
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PMID:Concomitant manifestation of systemic lupus erythematosus and low-grade non-Hodgkin's lymphoma. 926 88

To gain a better understanding of inherent gender-related effects on autoimmunity, cytokine genes were examined in female and male New Zealand Black X New Zealand White (B/W) mice, which are a murine model of systemic lupus erythematosus (SLE). In preliminary studies, semiquantitative reverse transcriptase-polymerase chain reaction analysis showed a trend for B/W spleen cell interferon gamma (IFN-gamma) mRNA in B/W female spleen cells to exceed that of males. This difference was obliterated following concanavalin A (Con A) stimulation. Spleen cells from B/W mice of both sexes were then examined at 6, 18, and 27 weeks of age, and results were compared with matched groups of nonautoimmune DBA/2 mice. Pooled splenocytes from all 12 groups of animals were compared simultaneously for expression of mRNA specific for IFN-gamma, interleukin 4 (IL-4) and interleukin 6 (IL-6). Strain was a potent influence on cytokine transcripts. In unstimulated splenocytes from female and male B/W mice, there was a notable trend for IFN-gamma and IL-6 mRNA expression to exceed transcripts from nonautoimmune DBA/2 mice. When comparisons were carried out by gender, a highly significant increase of IFN-gamma transcripts was apparent in B/W females compared to B/W males at the age of 27 weeks. Following Con A incubation, strain and gender differences were eliminated. IL-4 transcript expression was similar in all pools of cells, and age was not an important factor in expression of any transcript. This study represents the first examination of multiple cytokine transcripts in lymphoid cells from B/W mice. In this hormone-sensitive model of SLE, strain and gender determined in vivo expression of IFN-gamma and IL-6 mRNA.
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PMID:Cytokine mRNA expression in the B/W mouse model of systemic lupus erythematosus--analyses of strain, gender, and age effects. 928 84

We established a colony of MHC class I deleted (knockout) NZB mice, which lack the beta2 microglobulin gene (NZB.beta2m-/-), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33(+) cells, a marker of premature thymocyte maturation, was also seen in NZB.beta2m-/-. However, although NZB.beta2m-/- mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.beta2m-/- had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P-driven levels of IFN-gamma, IL-4, IL-6, and IL-12 in cells from NZB, NZB.beta-/-2, and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-gamma, and a marked increase in IL-6 and IL-12 in NZB and NZB.beta2m-/- mice.
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PMID:Autoantibody production and cytokine profiles of MHC class I (beta2-microglobulin) gene deleted New Zealand black (NZB) mice. 928 91

It has been previously reported that the production of interleukin-6 (IL-6) is often enhanced in systemic lupus erythematosus (SLE). The authors examined the secretion of IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor, IL-1 alpha and IL-4 by B cells and monocytes from lupus patients and compared this to the production in normal controls and in rheumatoid arthritis patients. IL-6 production was increased an average of 3.4-fold compared to that in normal subjects and 8.4-fold compared to rheumatoid arthritis patients. In SLE, a strongly positive correlation was found between the levels of IL-6 and TNF-alpha (R = 0.8987, P = 0.002). Since production of both IL-6 and TNF-alpha is regulated by IL-10, the enhancement of the production of these cytokines could reflect a defect in either IL-10 production or responsiveness. However, spontaneous production of IL-10 was enhanced in cultures of B cells and monocytes from lupus patients, compared to normal controls, the levels being increased 3.1- to 6-fold for monocytes and B cells, respectively. The finding of increased secretion of these cytokines implies an abnormality in IL-10-mediated suppression in SLE. To assess this possibility, the authors examined recombinant human IL-10-mediated suppression of IL-6 production by monocytes and B cells from lupus patients, compared to normal controls, and found that whereas IL-10 caused a concentration-dependent suppression of IL-6 production in normal B cells and monocytes, this suppression was deficient in B cells and monocytes from lupus patients. In SLE, it therefore appears that there may be an intrinsic defect in IL-10-induced suppression of cytokine synthesis. This could explain the increased levels of IL-10 and IL-6 found in this condition, and may also be responsible for the characteristic polyclonal B-cell activation that is seen.
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PMID:Interleukin-10 response abnormalities in systemic lupus erythematosus. 935 Feb 93

T cells with T cell receptor (TCR) transgenes that recognized CD1 on syngeneic B cells stimulated B cells to secrete immunoglobulins in vitro. The CD4+, CD8+, or CD4-CD8- T cells from the spleen of the TCR transgenic BALB/c donors induced lupus with anti-double stranded DNA antibodies, proteinuria, and immune complex glomerulonephritis in irradiated BALB/c nude mice reconstituted with nude bone marrow. Injection of purified CD4-CD8- T cells from the marrow of transgenic donors prevented the induction of lupus by the transgenic T cells. Transgenic T cells that induced lupus secreted large amounts of interferon (IFN)-gamma and little interleukin (IL)-4, and those that prevented lupus secreted large amounts of IL-4 and little IFN-gamma or IL-10.
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PMID:Subsets of transgenic T cells that recognize CD1 induce or prevent murine lupus: role of cytokines. 946 3

Polyclonal B-cell activation is the central theme in the production of autoantibodies and possible activation of autoreactive T cells in both human and murine lupus. The abnormal expansion of CD5+ B cells in murine lupus has been suggested, in particular, to be one of the most characteristic findings in these mice. Activated B cells can be separated from the B cells of resting stage by the difference in cell density. The aim of this study was to investigate the characteristics of different densities of the spleen cells separated by gradient density. Furthermore, the ability of anti-DNA antibody secretion in each percoll gradient fraction of B cells was also analysed. The results showed: a higher percentage of CD5+ B cells, which corresponded to the activated B-cell population, in percoll gradient 1 and 2 fractions; that splenic B cells of NZB/W F1 mice had proliferative response to interleukin (IL)-4 or IL-5 but not to IL-10 or interferon-gamma (IFN-gamma); and that B cells isolated by percoll gradient produced anti-DNA antibody after stimulation with lipopolysaccharide (LPS) plus IL-5 and IFN-gamma, but not IL-4 and IL-10. These data suggest that B cells at different stages of activation express differential characteristics and functions.
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PMID:Phenotypic and functional analysis of activated B cells of autoimmune NZB x NZW F1 mice. 949 86

In both mice and humans, functionally distinct helper T (Th)-cell subsets, known as Th1 and Th2 cells, are characterized by the patterns of cytokines they produce. These two polarized forms of the specific cellular immune response provide a useful model for explaining not only the different types of protection, but also the pathogenic mechanisms of several immunopathological disorders. The development of polarized Th1 or Th2 responses depends on either environmental factors, including dose of antigen, nature of immunogen and cytokines (IL-12 and interferons or IL-4) at the time of antigen presentation, or other undefined factors in the individual genetic background, mainly at level of the so-called "natural immunity". Th1-dominated responses are potentially effective in eradicating infectious agents, including those hidden within the host cells. When the Th1 response is poorly effective or exhaustively prolonged, it may result in host damage. In contrast, Th2 responses are apparently insufficient to protect against the majority of infectious agents, but can provide some protection against parasites. Th2 cells are able to make unpleasant the life of parasites in the host and tend to limit potentially harmful Th1-mediated responses. Thus, Th2 cells may be regarded as a part of down regulatory (or suppressor) mechanism for exaggerated and/ or inappropriate Th1 responses. The Th1/Th2 paradigm applied to the study of chronic inflammatory disorders or autoimmune diseases allowed to understand that a number of diseases are mediated by Th1 cells, the two clearest examples being multiple sclerosis and thyroid autoimmunity. In other disorders, Th1/Th2 polarization is less prominent, or rather Th2 responses tend to predominate, such as in systemic lupus erythematosus, progressive systemic sclerosis or allergic diseases. It is of note that in experimental models in animals, a number of diseases can be prevented by switching immune responses from Th1 to Th2 or from Th2 to Th1. Moreover, the Th1/Th2 concept suggests that modulation of the relative contribution of Th1- or Th2-type cytokines makes possible to regulate the balance between protection and immunopathology, as well as the development and/or the severity of some immunologic disorders.
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PMID:The concept of type-1 and type-2 helper T cells and their cytokines in humans. 950 98

An important prerequisite for a successful pregnancy is that the maternal immune system does not reject the fetus. Down-regulation of the T helper 1 (TH1) associated cellular immune response could therefore be essential. With flow cytometric techniques, we show on a single cell level that both CD4+ and CD8+ T cells from peripheral blood produce less TH1 cytokines (i.e. IFN-gamma and IL-2) and more TH2 cytokines (i.e. IL-4) during normal human pregnancy and shortly after delivery than during non-pregnancy. The TH1/TH2 cytokine ratio in T cells of women during pregnancy and after delivery was significantly decreased. In contrast the TH1/TH2 ratio was elevated to near normal in women with recurrent spontaneous abortions, indicating a marked shift towards TH1 immunity. Fas antigen (CD95) on T cells was significantly elevated during pregnancy and in the post-delivery phase whereas the intracellular expression of anti-apoptotic protein Bcl-2 remained unchanged. Nevertheless Fas-mediated apoptosis in T cells was markedly reduced during normal human pregnancy. We hypothesize that TH1 cells undergo predominantly Fas-mediated apoptosis during pregnancy as has been shown in some TH2-prone diseases (e.g. SLE, HIV) where an elevated Fas expression on peripheral T cells is observed. This could explain the exacerbated occurrence of TH2-associated diseases in pregnancy.
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PMID:Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes. 958 18


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