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)

Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal mice and mice with experimental autoimmune arthritis was studied with the patch-clamp whole-cell recording technique in combination with fluorescence microscopy. CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small numbers of type l or n' K+ channels, like their phenotypic counterparts in normal mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice, however, displayed an abundance of type l K+ channels compared to DN T cells in normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of type l K+ channels correlated with the presence of active disease. DN T cells from mice with SLE, type-1 diabetes mellitus, and experimental allergic encephalomyelitis, also exhibited a high number of type l K+ channels. These results suggest that expression of numerous type l K+ channels may be a useful marker for DN T cells associated with these autoimmune disorders.
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PMID:CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of type l K+ channels. 197 26

Changes in immune competent tissues of the HIV-1-infected person reflect to a certain extent the kind and intensity of immunological dysregulations. The diagnostic approach, however, must include immunophenotyping of cells, immunovirological studies of virus distribution in diseased tissues, and functional tests in addition to classical morphology. The latter technique alone just serves as a crude screening method since structural lesions in lymphoid tissues do not permit discrimination from other HIV-independent immune deficiency and autoimmune disorders. Although the overall appearance of lymph nodes in HIV infection and in chronic autoimmune disorders, such as collagen vascular diseases (e.g., rheumatoid arthritis and systemic lupus erythematosus), is similar, immunophenotyping shows a progressive loss of CD4 cells in HIV infection yet a quantitative increase in this cell population in autoimmune disorders (Krueger 1985a). In addition, there are other persistent active infections by lymphotropic viruses (e.g., EBV or HHV-6) which can cause structural and cellular changes in lymphoid tissues closely resembling HIV-induced lesions (Krueger et al. 1988b; Krueger 1985b). The pathological diagnosis therefore nedds to be supplemented by serological studies and--in selected cases--by in situ hybridization for the demonstration of viral genome. Southern blotting for viral DNA can only detect high numbers of viral genome copies in tissue extracts, not in which cell population the virus resides (e.g., malignant cells vs associated "normal" cells), while the polymerase chain amplification reaction, the most sensitive of all (Buchbinder et al. 1988), cannot yet differentiate between latent and (disease-related) active infection. Taking into consideration the above-described precautions in the evaluation of lymphatic lesions, there are a number of characteristic changes which reflect well the sequelae of HIV infection itself and of the ensuing immune dysregulation. Progressive loss of CD4 cells in the paracortex of lymph nodes and in the peripheral blood leads to inversion of the CD4/CD8 ratio. Loss of demonstrable CD4 cells is probably the consequence not only of cell lysis by HIV-1 infection (note: discrepancy between HIV-1 genome positive cell numbers and depletion of CD4 cells) but also of decreased CD4 marker synthesis in infected cells (Stevenson et al. 1987). In this context it is interesting that Fouchard et al. (1986) were able to show HIV expression in CD8 cells and theorized that these developed from infected CD4 cells which subsequently lost the CD4 epitope and expressed CD8.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunological dysregulation of lymph nodes in AIDS patients. 204 8

The purpose of the study was to determine the role of lymphocyte subsets (Ly) and reactive oxygen metabolites RSM, concerning the activity of BAL cells, in the pathogenesis of lung involvement in 12 patients with systemic sclerosis (SS) and 4 with systemic lupus erythematodes (SLE) in comparison with 10 control subjects. The cellular activity was measured by means of cytofluorometry (CFM) and chemiluminescence (CL). In SS/SLEY CD3+, CD4+, CD4/CD8-ratio, CD25 + T-Ly and luminol-dependent CL are increased (p less than 0.05). Correlations exist between CD3+, CD4+, CD8+ and CD25 + T-Ly and both luminol-dependent CL and neutrophils (p less than 0.01). The results suggest, that increased secretion of RSM by BAL-cells may be caused by local release of lymphokines by these activated T-Ly. Therefore CFM and CL seem to be useful in addition to BAL cell differentiation in characterizing the BAL cell activity in the diagnostic of lung involvement in SS and SLE.
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PMID:[Bronchoalveolar lavage in patients with systemic scleroderma and systemic lupus erythematosus: characterization of cell activity by cytofluorometry, chemiluminescence and differential cell count]. 205 69

L-Canavanine (LC) is an amino acid contained in alfalfa seeds that provokes a disease state similar to systemic lupus erythematosus (SLE) in primates. In vitro experiments showed that LC stimulated proliferation of human phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) and T cells of healthy donors but not of pokeweed mitogen (PWM)-stimulated PBMC. LC inhibited spontaneous generation of immunoglobulin-secreting cells (ISC) of PBMC, while it enhanced ISC generation of CD8(-) cells. LC inhibited PWM-induced ISC generation of CD8(-) cells but not of CD4(-) cells, indicating that LC stimulates CD8(-) cells more strongly than CD4(-) cells. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) was greater in CD8(-)Leu8(+) cells than CD8(-)Leu8(-) cells. The stimulation index was also higher in PBMC than in PBMC plus CD8(-)Leu8(-) cells, the former population containing relatively increased CD8(-)Leu8(+) cells. These findings suggest that LC acts mainly on CD8(-)Leu8(+) cells. That LC acts on CD8(-)Leu8(+) cells was confirmed by the finding that LC inhibited ISC generation of non-T plus CD4(+)Leu8(+), but not of non-T plus CD8(-)Leu8(-) cells. In addition, we found that PBMC of SLE patients were specifically unresponsive to LC stimulation. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) in SLE patients (n = 16) was 0.97 +/- 0.19, whereas that in age-matched healthy control (n = 17) was 1.45 +/- 0.40 (P less than 0.001). Patients with active disease were especially unresponsive to LC. Its responsiveness did not correlate with the dose of prednisolone administered. These findings suggest that the lymphocyte response to LC depends primarily on the existence of functional CD8(-)Leu8(+) cells. Moreover, it appears that suppressor-inducer T cells, responsive to LC, are especially deficient in SLE.
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PMID:L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine. 213 42

We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.
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PMID:Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro. 213 61

During a nationwide twin study on multiple sclerosis (MS) in Finland a dizygotic pair discordant for MS was found. The affected co-twin had dizygotic twin daughters. The affected co-twin of the second generation had systemic lupus erythematosus (SLE). Both pairs were thoroughly examined. No evidence of CNS involvement in the healthy co-twins was found. In pairwise comparisons, virus-specific IgG antibodies to measles and mumps were significantly increased in the MS patient whereas the same was true for rubella in the SLE patient. Both MS and SLE patient expressed HLA alleles most often found to be associated with these disorders. Reversed CD4/CD8 ratios were observed in both MS and SLE patient. No difference in interleukin-2 receptor expression were found but gamma-interferon secretion in the MS patient showed marked increase whereas that of the SLE patient was of the same magnitude as in the healthy members. A different triggering stimulus rather than the dissimilarity in the immunogenetic predisposition may be decisive as to whether or not they develop MS or SLE.
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PMID:MS and SLE in twins of successive generations. 235 74

Using the patch clamp whole-cell recording technique, we studied expression of K+ channels in mAb-defined T cell subsets from diseased C3H-lpr/lpr and C3H-gld/gld mice and from healthy C3H-HeJ congenic controls. Both mutant mouse strains develop a lupus-like syndrome accompanied by hyperplasia of a functionally and phenotypically abnormal T cell subset. These defective cells, which are Thy-1.2+ CD4- CD8- B220+ F23.1+, display an abundance of type l K+ channels. Phenotypically similar lymph node T cells from normal C3H-HeJ mice, or young C3H-lpr/lpr mice before the onset of disease, do not display large numbers of type l K+ channels. CD4+ CD8- T cells (helper/inducer) from the mutant mice express a small number of type n K+ channels, and CD4- CD8+ T cells (suppressor/cytotoxic) show a low level of type l or n' K+ channels, as do their phenotypically equivalent counterparts in the normal mouse thymus. These results suggest that the abundant expression of type l K+ channels is a marker for the defective lpr and gld T cell subset and may reflect the "abnormal" proliferative status of these cells.
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PMID:Abundant expression of type l K+ channels. A marker for lymphoproliferative diseases? 245 42

It is generally accepted that human Th cells express the surface glycoproteins CD4 and alpha/beta-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and alpha/beta TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the gamma/delta TCR; these cells can manifest MHC-restricted or nonrestricted cytotoxicity but no helper function. Herein we describe the existence of an unusual Th population in the peripheral blood of humans that are CD4-/CD8- and alpha/beta TCR+. These double-negative Th were markedly expanded in patients with the autoimmune disease SLE and along with CD4+ Th, they induced production of the pathogenic variety of anti-DNA autoantibodies that are IgG in class and cationic in charge. The cationic anti-DNA antibodies induced by the Th were markedly restricted in spectrotype indicating that an oligoclonal population of B cells were committed to produce the pathogenic autoantibodies in active lupus. IL-2-dependent T cell lines were also derived from the patients with active lupus nephritis but the majority of those T cell lines lacked pathogenic autoantibody-inducing capability. Only 4 out of 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA autoantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, alpha/beta TCR+ or CD4-/CD8-, alpha/beta TCR+. These studies suggest that production of pathogenic autoantibodies in human lupus is mediated by mechanisms that are distinct from the generalized, nonspecific polyclonal B cell hyperactivity that leads to excessive production of natural autoantibodies.
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PMID:T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis. 252 44

Our understanding of the immune mechanisms that lead to systemic lupus erythematosus has been greatly advanced by the availability of murine models which display both serological and clinical features of the human disease. Studies have demonstrated that CD4+ T cells are required for the full expression of disease in these mice. (NZB X NZW)F1 mice exhibit a lupus-like disease (elevated levels of IgG antinuclear antibodies and a fatal glomerulonephritis) that is not characteristic of either parent. At least three gene loci have been identified in NZW mice that could potentially contribute to a T cell-dependent autoimmune disease, including the T cell receptor alpha- and beta-chain gene complexes and the major histocompatibility complex (MHC). The NZW T cell receptor beta-chain complex appeared to be particularly unusual in that the C beta 1, D beta 2, and J beta 2 gene segments have been deleted. However, an analysis of (NZB X NZW)F1 X NZB back-cross mice revealed no association of disease expression with the presence of this allele. There was also no correlation of disease incidence with the presence of the NZW T cell receptor alpha-chain allele. In contrast, nearly 90% of the backcross mice with the NZW MHC expressed severe autoimmune disease compared with 12% of the mice that did not carry this haplotype. Additional studies strongly suggested that the gene(s) within the NZW MHC is the only dominant NZW genetic contribution to F1 disease. We also determined if self-reactive T cells are able to escape thymic tolerance in autoimmune New Zealand and MRLlpr/lpr mice. In nonautoimmune mice expressing I-E, T cells utilizing V beta 17a and V beta 11 encoded domains have been shown to be clonally eliminated in the thymus. Similarly, V beta 8.1+ and V beta 6+ T cells are tolerized in nonautoimmune mice expressing Mls-1a. These T cell subsets were quantified in the lymph nodes and spleens of (NZB X NZW)F1, (NZB X SWR)F1, and MRL-lpr/lpr mice before and after the development of lupus-like disease. The results indicate that peripheral T cells in these mice, including the massive CD4-, CD8- T cell population in lpr mice, have been modified by normal mechanisms of tolerance such that potential self-reactive V beta specificities have been eliminated in the thymus.
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PMID:Self-reactive T cells in murine lupus: analysis of genetic contributions and development of self-tolerance. 257 38

L-canavanine (LC) is an amino acid contained in alfalfa seeds that provokes a disease state similar to systemic lupus erythematosus (SLE) in primates. In vitro experiments show that LC mainly acts on CD8(-)Leu8(+) T cells to regulate antibody synthesis and lymphocyte proliferation. The lymphocytes of SLE patients were poorly responsive to LC stimulation, suggesting that CD8(-)Leu8(+) T cells are specifically deficient in SLE. Although the precise mechanism of intracellular action of LC is not yet clear, we found that the intracellular calcium level [( Ca2+]i) increased in response to LC. This increase in [Ca2+]i may be partially responsible for the mechanism of action of LC on lymphocytes.
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PMID:A study on immunological effects of L-canavanine. 263 43


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