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

A subset of normal peripheral B lymphocytes expresses a T surface antigen recognized by monoclonal CD5. They form rosettes with mouse erythrocytes (MRBC). Other studies suggest that these B cells may have regulatory and helper properties. An expanded subset of lymphocytes forming MRBC was demonstrated in the peripheral blood of 31 Systemic Lupus Erythematosus (SLE) patients (14.4 +/- 2.8%) compared with normal controls (4.3 +/- 1.4%) and patients with tuberculosis (6.4 +/- 1.7%). Increased MRBC values correlated with disease severity. Investigation of cell surface antigen expression was attempted with enriched sedimented fractions using several monoclonal antibodies and immunofluorescent staining. Complete inhibition of MRBC formation was obtained with monoclonal antibodies against CD5, CD3 and CD8 while partial inhibition was observed with anti-Ia and no activity with CD4 and CD10 antibodies. Indirect evidence supports the concept that antilymphocyte antibodies cause T and B cell depletion and dysfunction. Sera from 12 patients with SLE and 28 with leprosy (LL) were analyzed for antibodies to lymphocytes in the microcytotoxicity assay: 87% of SLE and 57% of LL were positive. Lymphocytotoxic activity towards each cell type of a panel with 98 different HLA antigens was essentially the same and most sera were not specific for either T or B cells. Lymphocytotoxic sera from SLE and LL contained antibodies which inhibited MRBC formation.
 ...
PMID:[Lymphocyte imbalance in autoimmunity]. 264 Apr 77

In 24 patients with systemic lupus erythematosus the proliferating response of lymphocytes of the peripheral blood stream to mitogens PHA, ConA and PWM was examined. The spontaneous incorporation of 3H-thymidine was increased in two patients. The mean response to PHA and PWM was reduced, while the response to ConA was within the normal range. In the active stage of the disease the lymphocyte response was in general lower in the stage of low activity. There was no correlation between the number of CD4 and CD8 lymphocytes nor the CD4/CD8 index and the lymphocyte response to mitogens. In systemic lupus erythematosus the response to PWM was lower than in rheumatoid arthritis, while in rheumatoid arthritis the response to PHA and ConA was lower than in systemic lupus erythematosus.
 ...
PMID:[Response of peripheral blood lymphocytes to antigenically nonspecific mitogens in systemic erythematosus]. 276 36

The T lymphocytes of patients with active systemic lupus erythematosus (SLE) exhibit impaired capping of the surface molecules CD3, CD4, and CD8 and a defective cAMP-dependent pathway. Since the mobility of these molecules is regulated in part by cAMP, we sought to determine whether there is a specific defect(s) along the T cell cAMP pathway that contributes to the persistent capping disorder observed during inactive SLE. The data suggest that a defect may exist at the level of cAMP-dependent protein kinase activation or at a point distally. We propose that a disorder of cAMP-dependent protein kinase activity might account for the defect of capping observed in both the CD3, CD4 (helper/inducer) and CD3, CD8 (suppressor) subsets observed in SLE.
 ...
PMID:Impaired mobility of human T lymphocyte surface molecules during inactive systemic lupus erythematosus. Relationship to a defective cAMP pathway. 283 Aug 91

This study was undertaken to examine the levels and function of peripheral blood immunoregulatory T cell subpopulations in systemic lupus erythematosus (SLE). T cell subpopulations can be distinguished by the T cell differentiation antigens CD4 (recognized by the monoclonal antibodies OKT4 or Leu3) and CD8 (recognized by the monoclonal antibodies OKT8 or Leu2). All SLE patients tested had normal percentages of CD8 cells in their peripheral blood. The SLE patients, however, fell into two groups based on their CD4 cell numbers. Fifty-five percent of the SLE patients had normal levels of CD4 cells (Group A) and therefore normal CD4/CD8 cell ratios, whereas 45% of the SLE patient population had markedly depressed CD4 cell levels (Group B) and significantly low CD4/CD8 cell ratios. T cells from normal donors and SLE patients were further examined for their ability to stimulate allogeneic normal B/M phi cells to secrete IgM in the presence of pokeweed mitogen (PWM). Utilizing this assay system two forms of immunosuppression were observed: (1) that mediated by high concentrations of purified CD4 cells and (2) that mediated by CD8 cells. High concentrations of purified CD4 cells, added to a constant number of allogeneic normal B/M phi cells, suppressed PWM-stimulated IgM synthesis. Group B SLE patients, with significantly low CD4 cell numbers, had defective CD4 cell-mediated suppression which was concentration dependent. This result was confirmed in a study using identical twins discordant for SLE. In this case CD4 cells from the SLE twin did not induce immunosuppression at a high concentration of CD4 cells whereas similar concentrations of CD4 cells from the normal twin resulted in suppression. SLE patients (Group A) with normal levels of CD4 cells had normally immunosuppressive CD4 cells. Suppression mediated by CD8 cells was demonstrated by the fact that removal of CD8 cells resulted in enhanced IgM synthesis induced by the remaining CD4 cells. Although all the SLE patients in this study had normal peripheral blood levels of CD8 cells, SLE Group A patients had defective CD8 cell suppression whereas CD8 function appeared to be normal in Group B patients. These results suggest that in SLE patients with depressed CD4 cell numbers (Group B) there is a corresponding defect in CD4 cell function. We demonstrate that in SLE Group B patients, defective suppression is due to a subset of T cells that bear the CD4 antigen. The SLE patient population (Group A) with normal CD4/CD8 ratios and normally functioning CD4 cells, however, appear to have normal CD4 cell-mediated suppression but defective CD8 suppressor cell function.
 ...
PMID:Two distinct subsets of patients with systemic lupus erythematosus. 297 Mar 55

IL-2 production by peripheral blood mononuclear cells (PBM) is decreased in patients with systemic lupus erythematosus (SLE). This defect can be reversed by the removal of CD8+ lymphocytes. The purpose of these studies was to determine whether the CD8+ IL-2 suppressor cells comprise a specific subset or whether all CD8+ cells have this activity. Lymphocyte subsets were identified and separated by two-colour flow cytometry prior to a 48 h mitogen stimulation. The CD8+ cells that suppressed IL-2 production co-expressed HLA DR and were radiosensitive. Other markers co-expressed by CD8+ cells which are found on suppressor cells such as Leu 15 (CD11), Leu 11 (CD16), and Leu 7 were also found on the CD8+ IL-2 suppressor cell population in SLE. In healthy subjects, removal of CD16+, but not of CD8+ cells markedly elevated the production of IL-2. The CD8- CD16+ non-T cell subset suppressed IL-2 production by normal and SLE PBM in autologous and allogeneic combinations. This subset may be a human equivalent of the murine natural suppressor cells. These results demonstrate that the cells that suppress IL-2 production in SLE are heterogeneous, and suggest that they belong to more than one lineage.
 ...
PMID:Characterization of lymphocytes that suppress IL-2 production in systemic lupus erythematosus. 297 25

The hypothesis that autoimmune diseases might be due to a defect in immunoregulation was tested in systemic lupus erythematosus (SLE). We have applied the double immunofluorescence, flow cytometry technique to peripheral blood lymphocytes from patients with SLE. T cells were studied for their binding of the lectin Vicia villosa (VV) which is a phenotypic marker for contra-suppressor cells both in mice and humans. A significant increase in CD3+VV+ and CD8+VV+ cells was found in patients with SLE, as compared with age and sex matched controls (P less than 0.01). When the patients were divided according to the 'lupus activity criteria count', those with active disease had a significantly increased proportion of CD3+VV+ and CD8+VV+ cells, as compared with those showing no disease activity (P less than 0.001). Indeed, a sequential investigation showed that the proportion of CD8+VV+ cells changed in parallel with exacerbation and remission of disease activity. These results suggest that disease activity in SLE is associated with an increase in VV binding CD8 cells which can function as contrasuppressor cells.
 ...
PMID:Phenotypic expression of Vicia villosa binding T cell subsets, as markers of contrasuppressor cells in systemic lupus erythematosus. 297 36

Biopsy specimens from mixed connective tissue disease (MCTD) and discoid lupus erythematodes (DLE) skin lesions were stained with monoclonal antibodies to differentiation and activation antigens. In addition, the blast cells were studied by combining autoradiography with immunoperoxidase staining. In both disease conditions most of the inflammatory cells in situ were positive for T11 antigen, the CD4/CD8 ratio being low. Only a few of the cells were pan-B positive B cells. The expression of various activation antigens did not differ significantly between MCTD and DLE biopsy specimens; the number of T9, Tac, and 4F2 antigen carrying cells was relatively low, whereas Ia-positive cells were more numerous. 3H-Thymidine incorporating T blasts comprised less than 1% of all inflammatory cells. T4 and T8 marker-carrying blast cells were present in about equal proportions. These findings suggest that Ia antigen-expressing T cells are important from the pathogenetic point of view in both MCTD and DLE. Because the local proliferation of T cells was extremely low according to the lack of interleukin-2 receptor and OKT9 markers and 3H-thymidine incorporation, it seems probable that most of the T cells are recruited from the circulation to the site of the inflammation.
 ...
PMID:Evaluation of lymphocyte activation in skin lesions of patients with mixed connective tissue disease and discoid lupus erythematodes. 325

Searching for the cause of the known immunological abnormalities in systemic lupus erythematosus (SLE), the density of cell surface antigens was measured after immunofluorescent staining in a cell sorter. The densities of CD3, CD4, CD5, CD8 and sIgM lymphocyte antigens were the same on patients' lymphocytes as on lymphocytes from healthy subjects. The intensity of HLA-DR immunofluorescence was found to be decreased on patients' monocytes, while the expression of HLA-DR on lymphocytes of patients with SLE hardly differed from that in healthy subjects. Pretreatment of normal mononuclear cells with patients' sera free from immune complexes decreased the binding of anti-HLA-DR antibody to normal monocytes, but it hardly caused alteration on lymphocytes. After culturing, the expression of HLA-DR antigen on patients' monocytes became the same as on normal cells. A causal role of anti-HLA-DR autoantibodies is suggested and discussed.
 ...
PMID:Antigen density on the surface of mononuclear cells in SLE. 331 77

Double-negative CD4-CD8-T cells (DNT) have been shown to be the major population of T cells responsible for the massive lymphadenopathy associated with the early onset of the lupus-like syndrome in mice bearing the lpr gene. Previously, we demonstrated that these cells do not proliferate in the peripheral lymphoid organs that they invade; furthermore, we showed that a wide range of CD4 Ag expression was observed on lymph node CD4+ T cells. In this study, we used an in vivo transfer system to analyze the progeny of CD4+ T cells from B6-lpr/lpr mice. Purified CD4+ T cells injected into B6 nude mice are able to generate DNT cells; furthermore, phenotypic and functional characterizations of the DNT cells generated in vivo show that they share the same properties as DNT cells from B6-lpr/lpr mice. We also show that, after in vitro bromodeoxyuridine incorporation, only CD4+ cells cycle. From these studies, we conclude that the lymphoproliferation occurs at the CD4+ stage and that down-regulation of this Ag probably is followed by arrest of the cell cycle.
 ...
PMID:In vivo CD4+ lymph node T cells from lpr mice generate CD4-CD8-B220+TCR-beta low cells. 752 11

Groups of female MRL/MpJ-lpr/lpr mice received either saline or FK506 (tacrolimus; 2 mg/kg intraperitoneally) three times weekly, cyclophosphamide (CY; 20 mg/kg) once monthly, or both drugs from 8 weeks of age. Median survival for untreated and CY-treated mice was 26 weeks, and for FK506- and FK506 + CY-treated groups was > or = 44 weeks. Severity of skin lesions and lymph node hyperplasia was markedly reduced by the drug combination, whereas either drug alone was less effective. FK506 or CY alone delayed the onset of proteinuria, but by 24 weeks all of these animals were positive. In contrast, drug combination reduced the prevalence of proteinuria to < or = 60% throughout the 44 weeks of study. Sequential monitoring of peripheral blood lymphocytes revealed that combination therapy but not monotherapy markedly reduced the proportion of atypical CD3+ B220+ and CD3+CD4-CD8- T cells. Neither FK506 nor CY affected the reduction in IL-2 and IL-4 mRNA levels observed in lymph nodes of diseased animals compared with normals. Although the drug combination also did not affect IL-2 mRNA levels, IL-4 mRNA transcripts were increased six-fold compared with saline-treated controls. IL-10 and interferon-gamma (IFN-gamma) mRNAs were induced by FK506, CY and by the drug combination. Serum levels of anti-dsDNA antibodies were reduced in all treatment groups. These data demonstrate improved efficacy of combined T and B cell-directed immunosuppression in murine lupus, associated with marked inhibition of atypical T cells and selective augmentation of IL-4 within the affected lymphoid tissue.
 ...
PMID:Combined effects of FK506 (tacrolimus) and cyclophosphamide on atypical B220+ T cells, cytokine gene expression and disease activity in MRL/MpJ-lpr/lpr mice. 753 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>