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 antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (approximately 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response.
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PMID:Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor. 214 99

The effect of plasma from 21 normal donors, 19 patients with non-Hodgkin's lymphoma and 11 patients with systemic lupus erythematosus (SLE) on interleukin 2 (IL-2) responsiveness, T cell proliferation and natural killer (NK) cell activity was studied. IL-2 responsiveness was enhanced by plasma from both normal and patients. The positive rate was 90.4% in normal, 89.5% in lymphoma and 90.9% in SLE, respectively. The same enhancing results were obtained in T cell proliferative assay. In contrast, effect of three kinds of plasma on NK cell activity showed inhibition. The inhibitory positive rate was 52.4% in normal, 36.8% in lymphoma and 81.8% in SLE, respectively. These results indicated that both enhancing and inhibitory effects on different immune functions showed certain specificity. The effect of plasmic substances on various immune responses is beneficial to the investigation of normal and abnormal immunoregulation. Furthermore, it is possible to isolate and purify these immunoregulatory substances as biological regulatory modifiers to modulate the abnormal immune functions.
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PMID:[Effect of plasma from normal individuals and lymphoma patients on immune function]. 224 92

Phytohemagglutinin (PHA) stimulated T cells from patients with systemic lupus erythematosus (SLE) showed hyporesponsiveness to interleukin 2 (IL-2) and expressed less p70/75 IL-2R than healthy controls. Ionomycine (IM, calcium ionophore) which selectively upregulated p70/75 expression, induced less p70/75 in patients with SLE than in healthy controls. However, intracellular calcium levels of T cells from patients with SLE increased as much as those from healthy controls, when T cells were stimulated by IM or PHA. Our results suggest that an impaired expression of p70/75 IL-2R in T cells from patients with SLE is not due to a defective calcium influx but to the events after the rise of calcium levels.
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PMID:Defective expression of p70/75 interleukin 2 receptor in T cells from patients with systemic lupus erythematosus: a possible defect in the process of increased intracellular calcium leading to p70/75 expression. 225 88

In patients with systemic lupus erythematosus (SLE), frequency of the T cells positive for HLA-DP, one of the major histocompatibility complex (MHC) class II molecules, was markedly increased in peripheral blood lymphocytes (PBL), in association with an increase in the amount of specific cytoplasmic transcript of the HLA-DP gene segment. Cell cycle analysis showed that HLA-DP is an early activation marker of T cells and that the high ratios of HLA-DP+ T cells from SLE patients are associated with high frequency of T cells at early activation phases, mainly of G1A. Initial high ratios of HLA-DP+ T cells decreased to a great extent during 4 days of in vitro culture, in the absence of mitogens. This event was associated with decreases in the amount of HLA-DP transcript and the disappearance of activated T cells. Studies on the interleukin 2 (IL-2) production of T cells from patients with SLE demonstrated that while the PBL rich in HLA-DP+ T cells show a markedly low production of IL-2, preculture of these PBL restores the ability to produce IL-2. Thus, it appears that the T cells in patients with SLE are essentially intact with regard to the capacity to produce IL-2 and that T cell activation events continuously occurring in SLE patients are related to a deficiency in IL-2 production. The possible underlying mechanisms are discussed.
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PMID:HLA-DP+ T cells and deficient interleukin-2 production in patients with systemic lupus erythematosus. 232 7

T-cell receptor gene rearrangement using a C beta probe was evaluated in 12 patients with rheumatoid arthritis, 2 with juvenile rheumatoid arthritis, and 1 with systemic lupus erythematosus, and in all the samples a dominant T-cell receptor gene rearrangement was noted. In rheumatoid arthritis identical T-cell receptor gene rearrangement was noted in freshly isolated synovial tissue-infiltrating lymphocytes (TIL) and the corresponding interleukin 2-propagated culture. TIL from five different joints obtained from one rheumatoid arthritis patient shared one dominant band, and TIL from three joints had an identical rearrangement. Limiting dilution experiments showed that 10% of T-cell clones had rearrangements matching the corresponding bulk in one rheumatoid arthritis patient. These findings lend further support to the suggestion that the clonal dominance noted among synovial tumor-infiltrating lymphocytes is the result of an in vivo process reflecting a selective T-cell receptor gene usage.
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PMID:Clonal dominance among synovial tissue-infiltrating lymphocytes in arthritis. 235 72

Polyclonal B cell activation is the most visible biological manifestation of systemic lupus erythematosus (SLE) autoimmunity. Murine models and in vitro lymphocyte studies are the most important tools used to improve our comprehension of the disease. It was successively demonstrated that there is an intrinsic B lymphocyte hyperreactivity in human and murine lupus; that the B lymphocytes overreact to stimulating factors produced by T lymphocytes; and that these stimulating factors could be over-produced. This last feature contrasts with decreased interleukin 2 production and lymphocyte response to this cytokine. A more precise study of the interleukins involved in the control of the humoral response shows the importance of interleukins 4, 5, 6 and of gamma-interferon. Further investigations are needed to improve our understanding of B cell hyperreactivity during SLE. These studies will benefit from better molecular characterization of many interleukins and their receptors.
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PMID:[B-lymphocyte hyperreactivity and differentiation factors of T-lymphocytes in systemic lupus erythematosus]. 236 9

Several murine strains with spontaneously occurring systemic lupus erythematosus-like disease demonstrate defects in immunoregulation. The MRL/MpJ-lpr/lpr (MRL-1) strain develops a severe age-progressive defect in interleukin 2 (IL 2) production in response to mitogen or antigen. In this study, we demonstrate in vitro the presence of suppressor cells in the lymph nodes of naive mice of the MRL background. Suppression by MRL-1 lymph node cells was partially reversed by treatment with anti-Lyt-1.2 monoclonal antibody and complement and was moderately radiosensitive. Suppression by lymph node cells from the congenic MRL/MpJ-+/+ (MRL-+) mouse was somewhat more resistant to treatment with anti-Lyt-1.2 and complement, or radiation. Lymph node cells from the H-2-syngeneic mouse strain, C3H/HeJ, failed to suppress. Thus, lymph nodes from mice of the MRL background contain cells capable of suppressing in vitro IL 2 responses. We next performed cell transfers to determine whether suppressor cells contribute in vivo to the IL 2 defect. Lymph node cells, but not spleen cells, from MRL-1 mice by 5 to 6 mo of age suppressed antigen-specific IL 2, CTL, and DTH responses when transferred into young MRL-+ recipients. Transfer of identical numbers of lymph node cells from age-matched MRL-+ mice failed to suppress IL 2 production. Transfer of suppression was sensitive to treatment with monoclonal anti-Lyt-2.1 and complement, and to 250 rad of radiation. Thus, this study suggests a role for active suppression of IL 2 production in the establishment of the IL 2 defect in the MRL-1 mouse. Further, suppression may involve phenotypically distinct T lymphocyte subpopulations.
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PMID:Suppression of antigen-specific interleukin 2 production in the MRL/MpJ-lpr/lpr mouse. 242 73

The T cell-associated antigen CD5 has been shown to play an important role in the regulation of T cell activation. Monoclonal antibodies directed against CD5 upregulate helper function, and induce interleukin 2 (IL2) production by mature T cells as well as thymocytes. CD5 is also expressed on subsets of B cells associated with autoantibody production, and CD5+ B cells are present in increased numbers in patients with rheumatoid arthritis and systemic lupus erythematosis. More recently CD5 has been found to be present on human B lymphocytes following in vitro activation with phorbol myristate acetate. To date a similar functional role for CD5 has not to date been demonstrated for B cells. In this study we have shown that structurally similar CD5 molecules are present on activated B cells and T cells. In addition, CD5 on both stimulated B cells and T cells is phosphorylated, which may be important in the function of CD5 following activation. CD5 protein or mRNA was not detected on unstimulated splenic B cells depleted of any CD5+ cells. To investigate the control of CD5 expression, we examined a series of cytokines either alone or in combination for their effect on the induction of CD5. CD5 expression was specifically inhibited by IL4 but not by the other cytokines tested. This inhibition was very specific as IL4 did not inhibit the expression of other B cell activation antigens including CD25, B5, T9 and CD23 as well as the pan-B cell antigen CD20. The addition of other cytokines did not increase or reverse the inhibition of CD5 expression by IL4. This inhibition was demonstrated by immunofluorescence and flow cytometric analysis. Immunoprecipitation studies of 125I-labeled activated B cells demonstrated that there was a decrease in cell surface CD5 protein, and not simply inhibition of expression of a particular epitope. Northern blot analysis demonstrated that the expression of CD5 mRNA was markedly inhibited in the presence of IL4, whereas the induction of the protooncogene c-myb was unaffected. This suggests that IL4 inhibits CD5 protein expression on activated B cells by reducing the amount of CD5 mRNA transcription or increasing the degradation of CD5 mRNA. The role of the T cell-derived lymphokine IL4 in regulating CD5 expression may be important in the disease states characterized by increased numbers of CD5+ B cells.
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PMID:Expression and regulation of CD5 on in vitro activated human B cells. 247 77

Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE.
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PMID:IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or systemic lupus erythematosus. 262 61

The recently described (Sharon, M. et al., Science 1986. 234:859) interleukin 2 (IL 2)-binding molecule p75 was detected in the CD3+4-8-Tac- "double-negative" cell population selectively expanded in lupus-like autoimmune mice MRL/MP-lpr/lpr using cross-linking studies. Scatchard analysis of the IL 2 binding revealed the existence of approximately 4700 sites per cell with an apparent Kd of 1500 pM. The cell line LD1.T3B, derived from this population, shared surface markers and the p75 presence/p55 absence of IL 2-binding proteins with its in vivo counterpart, displaying around 3100 sites per cell with a Kd of about 1300 pM. Functional studies showed that high doses of IL 2 had an inhibitory effect on the autonomous growth of this cell line in the absence of the development of killer activity. This study provides evidence of the functional abilities of p75, and shows that the use of Tac/p55 surface expression only to evaluate IL 2 receptors and T cell activation can be an oversimplification as well as misleading.
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PMID:Expression of the p75 interleukin 2-binding protein on CD3+4-8-Tac- cells from autoimmune MRL/MP-lpr/lpr mice. 278 6


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