Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive immunologic evaluation was made of a patient with severe systemic lupus erythematosus (SLE) undergoing 6 cycles of plasmapheresis combined with pulsed cyclophosphamide therapy. Clinical remission ensued accompanied by normalization of levels of circulating autoantibodies, immune complexes, complement proteins, interleukin 2 (IL-2) and IL-2 receptor. High spontaneous peripheral blood lymphocyte proliferation fluctuated widely with plasmapheresis, but was consistently reduced after cyclophosphamide. Circulating B cells fell by 85% and remained low at one year, despite recovery of the serum IgG level. Circulating T cells declined by 48%, chiefly in the immunologically naive CD4+CD45R+ T cell subset. This was associated with the emergence of a CD8+DR+CDw29+ T cell subset signifying immunologically mature, activated cytotoxic/suppressive T cells, which might have served to control the autoreactive B and T cell populations. Pulsed cyclophosphamide synchronized with plasmapheresis profoundly affected the immune system of our patient. The association of these immunological changes with clinical recovery warrants further investigation of this new therapeutic approach in SLE.
 ...
PMID:Immunologic effects of plasmapheresis synchronized with pulse cyclophosphamide in systemic lupus erythematosus. 182 61

T-cell-enriched populations obtained from lymph nodes (LNs) of 4-month-old MRL/Mp-lpr/lpr (MRL-lpr), C3H/HeJ-lpr/lpr (C3H-lpr), and C3H/HeJ-gld/gld (C3H-gld) mice were studied for the expression of B220, L3T4, and Lyt 2 antigens. A new B220+ L3T4+ phenotype was demonstrated in T-cell populations of these mice by two-color flow cytometry with phycoerythrin-conjugated monoclonal antibodies (MoAb) to L3T4 and FITC-anti-B220 MoAb. The generation of the T subset was apparently under the influence of the lpr or gld gene, since it could not be demonstrated in T-cell-enriched populations of MRL/Mp- +/+ and normal C3H mice. The expression level of L3T4 antigen on the T subset was lower than that on B220- L3T4+ cells, while the level of B220 antigen was similar to that of B220+ L3T4- or B220+ Lyt 2- cells. The B220+ L3T4+ phenotype appeared in LNs and spleens, but not in thymuses, of MRL-lpr mice as early as 2 months of age. Its proportion to whole LN T cells at this age was equivalent to that observed in 4-month-old mice. Functional studies on FACS-sorted cell populations revealed that the T subset similar to B220+ L3T4- cells possessed deficiencies in the IL-2-IL-2 receptor system. The appearance of the T subset with an intermediate phenotype and its functional defects suggests that lpr and gld genes in these autoimmune mice exert their influences on the ontogeny and function of L3T4+ T cells and contribute to the induction of early lupus.
 ...
PMID:Ontogeny and function of B220+ L3T4+ T-cell subset of MRL/Mp-lpr/lpr mice. 245 58

Our results provide important evidence that IL-2 receptor bearing cells are required for undesired immune reactions involved in autoimmunity, allograft rejection and nephritogenic processes. Administration of anti-IL-2 receptor monoclonal antibodies prolonged vascularized heart allograft survival across major histocompatibility barrier in mice and rats and renal monkey grafts. Indeed, several grafts survived indefinitely, although the antibody was administered only for the first 10 days post-transplantation. Rejection of the remaining grafts may well reflect inadequate dosage of antibody; dose-response studies have not been performed to date. In addition to preventing rejection, delayed treatment with anti-IL-2R monoclonal antibody was shown to reverse ongoing rejection in other recipients of heart allografts. Such long-term engraftment following cessation of therapy makes it unlikely that anti-IL-2R treatment prolongs graft survival by pharmacologic blockade of the IL-2R. Furthermore, exogenous IL-2 does not diminish the beneficial effects of anti-IL-2R antibody therapy in rodents. Whether or not such prolonged graft survival represents deletion of the responding T cell clones is a subject of current investigation. Results in a delayed-type hypersensitivity model indicate that complement fixation, is required to achieve optimal immunosuppression. Moreover, only anti-receptor antibodies that block IL-2 binding mediate optimal immunosuppression. Passive transfer experiments clearly prove that immediate post-transplant courses of anti-IL-2R monoclonal antibody spares suppressor T cells. In rodent models, delayed type hypersensitivity and lupus and diabetic autoimmunity are prevented by anti-IL-2R treatment. Finally, the availability of monoclonal antibodies directed against the human IL-2R provides an opportunity to extend this principle to clinical transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Toward more selective therapies to block undesired immune responses. 265 66

Sera obtained from patients with systemic lupus erythematosus (SLE) were tested for their reactivity to cell lines derived from cutaneous T-cell lymphoma (CTCL), or adult T cell leukaemia (ATL), and with other cell lines, by indirect immunofluorescence method. Approximately one half of SLE sera reacted with the surface antigens of HUT-102 cells, a cell line from CTCL, which constitutively expresses Tac antigen. The titre tended to be higher in the active than in the inactive stage. These positive sera also reacted with other neoplastic or normal T cell lines having Tac antigen. SLE sera reacting with HUT-102 surface antigens were further examined for their reactivities to Tac antigen, the putative IL-2 receptor, using HUT-102 or ATL-2. Pretreatment with anti-Tac monoclonal antibody partially blocked the reactivities to HUT-102 surface antigens in nine of 15 SLE sera tested. The binding of 125I-labelled anti-Tac monoclonal antibody was displaced by the addition of sera from six of 15 SLE patients. In addition, nine of the 15 SLE sera could inhibit the binding of 125I-labelled IL-2 to ATL-2 cells. These results suggested that some of SLE sera contained antibodies against the IL-2 receptor.
 ...
PMID:Systemic lupus erythematosus sera antilymphocyte reactivity: detection of antibodies to Tac-antigen positive T cell lines. 300 53

Activated T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE) were determined using monoclonal antibodies against activation antigens. Elevated percentages of HLA-DR+ T cells were found in association with active disease. In contrast, we observed an increase in IL-2 receptor-bearing T cells in only six out of 16 patients with active disease. In vitro assays, like spontaneous proliferation, response to IL-2, production of IL-2, and immunoglobulin synthesis have shown that the different patterns of activation antigens are related to different functional stages of T-cell activation. The possible therapeutic consequences are discussed.
 ...
PMID:Correlation between the phenotype and the functional capacity of activated T cells in patients with active systemic lupus erythematosus. 301 41

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.
 ...
PMID:Impaired expression of high affinity interleukin 2 receptor on activated lymphocytes from patients with systemic lupus erythematosus. 311 22

IgG antilymphocyte antibodies preferentially reacting with phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) and an adult T cell leukemia cell line were detected in 70.6% sera from patients with systemic lupus erythematosus (SLE), using a fluorescence activated cell sorter (FACS). In the sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, 2 major peaks with an apparent molecular weight 60,000 to 65,000 Da and about 40,000 Da were observed in the membrane glycoprotein fractions of both PHA activated PBL and an adult T cell leukemia cell line. From the result of sequential coprecipitation analysis of SDS-PAGE between SLE serum, antiinterleukin-2 (IL-2) receptor antibody (anti-Tac antibody) and anti-Ia antibody, the reactive antigen on the activated PBL and an adult T cell leukemia cell line proved to be an identical molecule of the IL-2 receptor on these cells. The role of this autoantibody in the modulation of T cell mediated immunity in patients with SLE is discussed.
 ...
PMID:Antibody to activated lymphocytes in patients with systemic lupus erythematosus. 312 75

Peripheral blood lymphocytes from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), Reiter's disease, osteoarthritis, and from healthy volunteers were investigated for interferon-gamma (IFN-gamma) production after mitogen activation. Phytohaemagglutinin stimulation revealed an impaired IFN-gamma production in RA, SLE, and PSS but normal levels in Reiter's disease and osteoarthritis. In RA this deficiency was also seen after pokeweed mitogen, OKT3, and concanavalin A activation. No major differences were found in interleukin 2 (IL-2) production and cell proliferation. The IL-2 receptor expression was reduced on stimulated RA lymphocytes. The deficient IFN-gamma production was compensated in RA by co-stimulation of PHA or OKT3 with phorbol myristic acetate (PMA). In addition, the combination of the calcium ionophore A 23187 and PMA induced a strong IFN-gamma secretion in all patient groups and in the controls.
 ...
PMID:Impaired mitogen-induced interferon-gamma production in rheumatoid arthritis and related diseases. 312 62

Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.
 ...
PMID:Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma. 312 92

Deficient interleukin-2 (IL-2) production and other T-cell dysfunctions have been demonstrated in active systemic lupus erythematosus (SLE). The generation of IL-2 receptors is known to be important to the growth and differentiation of T and B lymphocytes. This study investigated IL-2 receptor expression in peripheral blood lymphocytes (PBL) from patients with active and inactive SLE. PBL from 27 SLE patients, diagnosed by revised ARA criteria, were assayed for IL-2 receptor expression, IL-2 and immunoglobulin (Ig) production. PBL from SLE patients with active disease spontaneously expressed increased numbers of IL-2 receptors compared to those with inactive disease (P less than 0.01) and normal donors (P less than 0.01). There was no significant increase in IL-2 receptors expression in PBL from active SLE patients in response to mitogenic stimulation with PHA compared to inactive SLE patients and normal donors. There was negligible IL-2 production in response to mitogenic stimulation and increased spontaneous IgG production by PBL from active SLE patients compared to normal donors (P less than 0.001). Purified B cells isolated from active SLE patients showed significant spontaneous IL-2 receptor expression when compared to spontaneous IL-2 receptor expression by normal B cells (P = 0.005). Therefore, in addition to derangements in Ig and IL-2 production, the level of spontaneous expression of IL-2 receptors may represent a cellular indicator of disease activity, and hence, may be a useful parameter in monitoring disease activity in SLE patients. The significance of the increased IL-2 receptor expression on B cells of active SLE patients is unknown, but may represent a marker of polyclonal activation of these cells.
 ...
PMID:Interleukin-2 receptor expression in peripheral blood lymphocytes from systemic lupus erythematosus patients: relationship to clinical activity. 313 Oct 53


1 2 3 4 5 6 Next >>