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)

During autologous mixed lymphocyte reaction (AMLR) both helper and suppressor T cells capable of regulating B cell responses are generated. The proliferative response of T cells as well as the generation of T suppressor cells in the AMLR of patients with active systemic lupus erythematosus (SLE) is diminished. In contrast, the T helper cells generated in the AMLR show a hyperactivity. The diminished HLA-class II antigen expression observed on non-T cells of SLE origin was restored by treatment of the cells with gamma-interferon (gamma-IFN). When tested by immunoglobulin secretion, gamma-IFN enhanced T helper cell activity but failed to affect T cell proliferation and T suppressor cell generation in the AMLR derived from patients with SLE. Human recombinant interleukin 2 restores both the proliferative response of T cells and the induction of T suppressor cells in AMLR.
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PMID:IL-2 normalizes defective suppressor T cell function of patients with systemic lupus erythematosus in vitro. 295 81

BXSB male mice serve as one of several murine models of human systemic lupus erythematosus. T-cell abnormalities in these mice involve decreased production of and responsiveness interleukin 2 (IL-2) and are age-related. The studies presented here investigated the mechanism of these T-cell defects. The results suggest that excessive suppressor-T-cell activity as well as soluble inhibitors of IL-2 production and activity, including PGE, are not responsible for the low levels of IL-2 observed in culture supernatants of Con A-stimulated lymphocytes from "old" (3-6 months) BXSB male mice. Supplementation of Con A-stimulated lymphocyte cultures from BXSB male mice with human IL-1 or normal murine accessory cells did not augment IL-2 production. Reduced proliferative responses were observed in bulk cultures of Con A- or alloantigen-stimulated "old" BXSB male lymphocytes, which were not enhanced by exogenous IL-2. Limiting dilution analysis revealed reduced frequencies of Con A- and alloantigen-inducible IL-2-reactive T cells in these mice. These results suggest intrinsic defects in the ability of T cells from "old" BXSB male mice to be activated to produce and respond to IL-2.
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PMID:Production of and responsiveness to interleukin 2 in autoimmune BXSB mice. 295 44

CD8+ lymphocytes comprise several cell subpopulations that differ phenotypically and functionally. Although the percentage of T cytotoxic/suppressor cells (CD3+ CD8+) is usually increased in patients with active SLE, these lymphocytes are unable to suppress immunoglobulin (Ig) synthesis. However, freshly prepared lymphocytes from patients with SLE contain CD8+ DR+ cells which spontaneously suppress lymphocyte production of mitogen induced interleukin 2 (IL-2). Furthermore, CD8+ Leu 11+ non-T cells which comprise only 5% of total lymphocytes are also potent suppressors of IL-2 production. At the present time it is not known whether CD8+ suppressors of Ig synthesis and CD8+ suppressors of IL-2 production represent different maturation stages of common precursor cells or represent true heterogeneity of CD8+ lymphocytes.
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PMID:Functional properties of CD8 positive lymphocyte subsets in systemic lupus erythematosus. 295 20

In an effort to characterize further the role of T cells in the autoimmune disease of MRL/Mp-lpr/lpr (lpr) mice, continuous cell lines were established from spleen and lymph nodes using EL-4 lymphoma supernatants as a source of T-cell growth factor(s). Five lines were derived from lpr spleen and lymph nodes, and an equal number from MRL/Mp- +/+ (+/+). All of the lines lost their alloreactivity after a short time in culture. Surprisingly, every line manifested marked proliferation in response to autologous irradiated spleen cells. This response was restricted to I-Ak, as it was blocked with monoclonal anti-I-Ak antibodies, and as B10.A(4R) accessory cells were stimulatory while B10.A(3R) were not. There was no difference in the degree of stimulation from lpr accessory cells compared to that in those from +/+ or other H-2k mice. The T-cell lines bore Thy-1, Ly-1, L3T4, and 7D4 (interleukin 2 (IL-2) receptor), but lacked Ly-2 and surface Ig. They proliferated in response to both conventional and recombinant DNA-derived IL-2. When cocultured with Ia-identical B cells, the T-cell lines provoked B-cell division and antibody production. The cells also caused intense proliferation when cultured with freshly isolated lpr (but not +/+) lymph node cells. The results indicate that lpr lymphoid tissue contains functional T cells reactive to autologous Ia molecules and capable of inducing both B-cell activation and the proliferation of lpr lymphocytes. Such cells may be of importance in inducing hypergammaglobulinemia, autoantibody production, and lymphoproliferation in these SLE mice.
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PMID:Characterization of functional T-cell lines derived from MRL mice. 308 56

T cells from murine lupus strains manifest complex defects in interleukin 2 (IL 2) production and receptor expression. The capacity of B cells from such mice to utilize IL 2 as a growth factor has not been previously reported and is examined herein. Anti-Thy-1.2 plus complement-treated spleen cells from 6-8-week-old autoimmune MRL-lpr/lpr mice and from age and sex-matched immunologically normal CBA/J mice were cultured with lipopolysaccharide (LPS) for 36 h and analyzed for the expression of IL 2 receptors using the monoclonal antibody 7D4. The percentage of B cells expressing IL 2 receptors was comparable in MRL-lpr/lpr and CBA/J mice. In contrast to those from CBA/J, BALB/c and (BALB/c X NZW)F1 mice, LPS-stimulated B cells from MRL-lpr/lpr and from (NZB X NZW)F1 mice were capable of proliferating in response to IL 2. Fractionation of MRL-lpr/lpr B cells using Percoll gradient density separation demonstrated that the IL 2-responsive population consisted predominantly of large cells. In addition, unfractionated B cells from MRL-lpr/lpr mice were found to be substantially more responsive to IL 2 than those from CBA/J and BALB/c mice following activation with anti-immunoglobulin plus LPS. The hyper-responsiveness to IL 2 may be a consequence of the state of activation of autoimmune B cells and is of potential importance in the pathogenesis of systemic lupus erythematosus.
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PMID:Interleukin 2 is a proliferative signal for B cells from autoimmune mice. 309 46

Defects in interleukin 2 (IL2) responsiveness may contribute to immunologic abnormalities in systemic lupus erythematosus (SLE). We studied the acquisition of IL2 receptors and responsiveness to recombinant human IL2 (rIL2) in the peripheral blood mononuclear cells (PBM) of patients with SLE and matched control subjects. Peak rIL2-induced proliferation was significantly decreased (mean reduction of 58%) in 5 of the 10 patients with SLE. Five of six patients with SLE studied for phytohemagglutinin-induced IL2 receptors had acquisition of IL2 receptors comparable to that of the control subjects. Some patients with SLE have a defect in rIL2-induced proliferation of their "resting" PBM that seems unrelated to a concomitant defect in phytohemagglutinin-induced IL2 receptor acquisition. This finding suggests that the defect in rIL2-induced proliferation may be due to either an abnormality in postreceptor signaling or an impairment in induction of high-affinity IL2 receptors.
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PMID:Interleukin 2 receptors and responsiveness to recombinant human interleukin 2 in patients with systemic lupus erythematosus. 309 2

Peripheral lymphocytes stimulated with phytohemagglutinin (PHA-blasts) were examined for their responsiveness to exogenous interleukin 2 (IL-2). The proliferative response of PHA-blasts to IL-2 was significantly lower in patients with systemic lupus erythematosus (SLE) than in normal subjects. To clarify the reason for this defect, the expression of IL-2 receptor (IL-2R) on PHA-blasts was investigated using anti-Tac antibody and purified IL-2. Cytofluorometric analysis showed no statistical differences in the Tac positivity of PHA-blasts among normal subjects and patients with active and inactive SLE. Scatchard analysis using 125I-labeled anti-Tac monoclonal antibody revealed that the number of Tac epitopes on PHA-blasts was also not different among them. Next, the affinity of IL-2R expressed on PHA-blasts was determined by Scatchard analysis using radiolabeled IL-2 as a ligand. The number of high affinity IL-2R on the PHA-blasts was significantly decreased in patients with active and inactive SLE, as compared with normal subjects. The responsiveness of PHA-blasts to exogenous IL-2 was well correlated to the number of high affinity IL-2R, but not to the number of Tac epitopes or total IL-2R. Inasmuch as high affinity components of IL-2R are functionally active, the defective expression of high affinity IL-2R may be responsible for the T cell dysfunctions in SLE.
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PMID:Impaired expression of high affinity interleukin 2 receptor on activated lymphocytes from patients with systemic lupus erythematosus. 311 22

Systemic lupus erythematosus (SLE) is a disease of immune dysregulation in which B cell hyperactivity and T cell deficiency are important characteristics. Sex factors also play a major role in the pathogenesis based on the physiologic effects of estrogen in promoting immunologic hyperactivity. Our findings suggest that a posttranscriptional mechanism is responsible for the functional interleukin 2 (IL-2) defect since transcription of the IL-2 message occurs after mitogenic stimulation. The proliferating cell in the MRL/lpr mouse model of lupus may be an immature T cell. The T cell receptor in these mice has a lower molecular weight than normal. This aberrant T cell receptor might be explained by a defect in glycosylation. The administration of estrogen to pregnant mice late in gestation results in offspring with a permanently altered immune system. These mice develop features of autoimmunity similar to those that occur spontaneously in genetically susceptible autoimmune mice. This phenomenon may have etiopathological significance for familial SLE.
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PMID:Interleukin 2, T cell receptor and sex hormone studies in autoimmune mice. 311 77

Mice which bear the lpr gene spontaneously develop autoimmune syndromes characterized by massive expansion of an unusual T cell subset which is phenotypically Thy-1+, L3T4-, Lyt-2-, B220+. The mutant T cells are refractory to stimulation with mitogenic lectins and, by implication, are thought to be solely responsible for the defects in lymphokine production manifested by lpr mice. The contribution of the remaining L3T4+ T cell subset to the latter derangements has not been previously examined and is the focus of this study. We found that abnormalities in concanavalin A-induced interleukin 2 and 3 production in the spleens of MRL-lpr/lpr and C57BL/6.lpr mice occurred in the presence of limited infiltration with B220+, L3T4- T cells. Mixing experiments indicated that B220+ T cells were not suppressive. Furthermore, lpr spleen cells enriched for L3T4+ cells and depleted of sIg+, B220+ and Lyt-2+ cells demonstrated reductions in lymphokine production which were comparable to those seen in unfractionated preparations. Spleen cells from C57BL/6.lpr mice, enriched for L3T4+ cells, were also markedly impaired in a mixed leukocyte reaction in response to stimulator cells from the class II major histocompatibility complex mutant bm12. The results indicate that the aberrations in lymphokine production and proliferation in the spleen cells of lpr mice involve not only B220+ T cells but also L3T4+ cells and suggest a potential role for the L3T4+ subset in the pathogenesis of lupus in lpr-bearing mice.
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PMID:The role of L3T4+ cells in the pathogenesis of lupus in lpr-bearing mice. I. Defects in the production of interleukins 2 and 3. 311 78

Activation/proliferation of mouse and human T and B cells is associated with expression and subsequent release of interleukin 2 receptors (IL 2R) into the milieu. The soluble form of IL 2R, at least in part, retains its ability to bind to IL 2 and to anti-receptor antibodies, but its exact structure remains unknown. Because systemic lupus erythematosus (SLE) is associated with T and B cell activation, we have used monoclonal anti-IL 2R antibodies in an ELISA to measure levels of IL 2R in sera of various lupus strains. High levels of the released receptor were found at an active clinical stage in sera of four autoimmune strains of mice homozygous for the lpr (lymphoproliferation) gene that causes T cell expansion, massive lymphoid organ enlargement, and promotes the autoimmune process. High levels were also found in lupus mice characterized primarily by B cell proliferation (BXSB males) and in (NZB X W)F1 mice characterized by T and B cell activation. Similarly high IL 2R serum levels could be induced experimentally in normal mice injected with immunostimulants such as bacterial lipopolysaccharide or Freund's complete adjuvant. The results indicate that IL 2R serum levels may provide a good marker of ongoing lymphoid cell activation/proliferation, and thus might be useful in the follow-up of patients with systemic autoimmune or other lymphoproliferative disorders. The biologic roles, if any, of the soluble form of IL 2R and its effects in normal and abnormal conditions remain to be determined.
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PMID:Elevated titers of cell-free interleukin 2 receptor in serum of lupus mice. 311 68


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