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)

The effect of polyclonal (anti alpha and beta chain) and monoclonal (anti alpha-chain) antibodies against lymphocyte function-associated antigen 1 (LFA-1) on T cell activation was studied. When added at the beginning of activation but not after 24 h or later the antibodies as well as the F(ab')2 or Fab fragments of polyclonal antibodies inhibited concanavalin A (Con A)-induced proliferation, interleukin 2 (IL-2) production, and the expression of receptors for IL-2 and transferrin. The inhibitory effect reached a maximum at the same time as optimal proliferation (72 h). Inhibition of proliferation lasted for 5 days or longer, although IL-2 production was only inhibited during the first 48 h of culture. Receptors for IL-2 and transferrin were re-expressed to the original level after 3 days of activation. Addition of external IL-2 at the beginning of the anti-LFA-1 containing culture prevented the inhibition of IL-2 receptor expression, while inhibition of transferrin receptor expression was unaffected, supporting the conclusion that the expression of these two receptors is regulated by partially independent signals. The polyclonal and monoclonal anti-LFA-1 antibodies also inhibited phorbol ester (PMA)-dependent OKT3 activation of highly purified T cells. The results suggest that the LFA-1 antibodies block an early step in the reactions necessary for IL-2 production, and that the LFA-1 molecule participates not only in T cell-accessory cell interaction but also in T-T interaction during the early phases of the activation process.
 ...
PMID:Studies on the role of lymphocyte function-associated antigen 1 (LFA-1) in T cell activation. 312 61

Low and high affinity receptors for interleukin 2 were investigated on interleukin 2 (IL-2) receptor bearing cells by chemical cross-linking of 125I-labelled IL-2 to its receptor, or membrane proteins associated with the IL-2 binding sites. SDS-PAGE analysis of the cross-linked complexes of the murine CTLL 16 cells and human T-blasts, which bear high and low affinity IL-2 receptors, showed three distinct bands. The fastest of those three bands ran in parallel to the single band of 65-70 kDa found on the only low affinity receptor bearing mouse T-lymphoma Eb, which is thought to be one beta-chain (55 kDa IL-2 binding protein) and one IL-2. Both upper bands ran in parallel with those produced by the 2C8 clone of the NK-like cell line YT which lacks the 55 kDa binding protein and bears only a single class of receptors with an intermediate affinity. Internalisation studies using CTLL 16 cells revealed that all three bands disappeared under conditions allowing receptor internalisation. Low and high affinity binding sites of CTLL 16 cells were destroyed by trypsinisation and the IL-2 binding properties of the cells were regenerated in parallel with the reappearance of all bands. These results show in addition to the beta-chain (55 kDa binding protein) and the alpha-chain 75 kDa binding protein, an IL-2 membrane protein complex with an apparent mol. wt of 115 kDa in CTLL 16 cells. They are the first direct indication of a putative gamma-chain of the high affinity IL-2 receptor.
 ...
PMID:The high affinity interleukin 2 receptor: evidence for three distinct polypeptide chains comprising the high affinity interleukin 2 receptor. 326 78

FK 506 is a new immunosuppressive agent with a similar molecular action to cyclosporin A. We have investigated immunohistochemical changes in lesional biopsies of seven patients with severe recalcitrant chronic plaque psoriasis receiving systemic FK 506 therapy. Within 4 weeks of start of treatment, there was a striking reduction in psoriasis area and severity index (mean reduction 87.4%), accompanied by marked reductions in dermal and epidermal CD4+ and CD8+ cells. Investigation of biopsies obtained 4-8 weeks after start of treatment revealed a significant fall in the numbers of activated mononuclear cells expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte function-associated antigen-1, LFA-1 alpha chain). In contrast, the number of epidermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study of leukocyte adhesion-related epitopes in active disease revealed strong expression of CD54 (intercellular adhesion molecule-1, ICAM-1) and E-selectin (previously known as endothelial leukocyte adhesion molecule-1) both on microvascular endothelial cells and of ICAM-1 on infiltrating mononuclear cells; ICAM-1 was also expressed weakly on epidermal keratinocytes. Vascular cell adhesion molecule-1 (VCAM-1) was either absent or expressed rarely on vascular endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin expression on blood vessels was reduced consistently but nevertheless persisted, even in individuals exhibiting total clearance of psoriatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:ICAM-1 and E-selectin expression in lesional biopsies of psoriasis patients responding to systemic FK 506 therapy. 750 32

Interleukin (IL)-2, initially discovered for its mitogenic activity on T cells, also acts on monocytes, resulting in the activation of cytokine production, superoxide production, and tumoricidal activity. Because severe brain damage was observed in IL-2-transgenic mice, this cytokine may have some influence(s) on the cells of the CNS. We investigated IL-2 receptor-bearing cells in the CNS and found that activated microglia expressed alpha-chain mRNA and immunoreactive IL-2 receptor beta-chain protein in culture. Although microglia did not express IL-2 receptors under normal culture conditions, they were induced to express these receptors by lipopolysaccharide (LPS) in a time-dependent manner. The IL-2 receptors were found to be functional because the viability and growth activity of LPS-treated microglia, but not untreated controls, increased in response to recombinant mouse IL-2 as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and bromodeoxyuridine uptake experiment, respectively. These effects of recombinant IL-2 were blocked by pretreatment with anti-mouse IL-2 receptor beta-chain antibody. Our findings suggest that activated microglia in the CNS can respond to this T cell-derived factor regulating their growth, which may be an important mechanism of communication between nervous and immune systems in physiological and pathological conditions.
 ...
PMID:Induction of functional interleukin-2 receptor in mouse microglia. 753

One of the most central events during lymphocyte activation is the synthesis and release of IL-2. IL-2 induces the synthesis and expression of the IL-2 receptor alpha-chain (IL-2R) on the lymphocyte as well as the release of a truncated form of IL-2R (sIL-2R). The two proteins are identical except for the absence of the transmembrane and intracellular part on sIL-2R. We have in an in vitro model investigated the influence of certain compounds, affecting different parts of the proliferative response, on the release and expression of IL-2R. We found the generation of the two molecules to have different sensitivity to blocking of protein synthesis, glycosylation, microtubular assembly and proteolytic activity. However, blocking of intracellular transport from Golgi to the endoplasmic reticulum, disassembly of actin filaments and disturbances in the intracellular sodium/calcium balance had identical effects on expression and release of the respective IL-2R. These findings indicate a more complex and specific mechanism behind the generation of sIL-2R than simply by shedding through the action of proteases on the membrane-bound IL-2R.
 ...
PMID:Influence of compounds affecting synthesis, modification and transport of proteins on the expression and release of interleukin-2 receptor. 753 4

It has previously been described that V gamma 3 cells can proliferate extensively in vitro in the presence of different cytokines. Here, the role of cytokines in the maintenance of V gamma 3 cells in the thymus has been determined. Culture of fetal thymocytes in cell suspension for 24 h showed that, whereas immature TCRlowHSAhigh V gamma 3 cells remained viable, all mature TCRhighHSAlow V gamma 3 cells died. These cells died by apoptosis since protein synthesis was required and flow cytometric analysis as well as DNA gel electrophoresis showed that the DNA was degraded to oligonucleosomal bands. Addition of IL-2, IL-4 or IL-7 to suspension cultures of fetal thymocytes rescued V gamma 3 cells from dying. Addition of IL-1, IL-3, IL-5, IL-6, IL-9, TNF-alpha or IFN-gamma was without effect. Phenotypic analysis showed that the alpha-chain of the IL-2 receptor (IL-2R alpha) was expressed by part of the immature V gamma 3 thymocytes, all mature V gamma 3 cells expressed the beta-chain of the IL-2 receptor (IL-2R beta). Addition of anti-IL-2R beta mAb to fetal thymic organ culture (FTOC) resulted in a moderate reduction of the cell number of mature V gamma 3 thymocytes. Addition of anti-IL-2R alpha, anti-IL-4 or anti-IL-7 mAb had no effect. The cell number of mature V gamma 3 cells was highly reduced when both anti-IL-2R beta and anti-IL-7 mAb were added to FTOC.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytokine dependence of V gamma 3 thymocytes: mature but not immature V gamma 3 cells require endogenous IL-2 and IL-7 to survive--evidence for cytokine redundancy. 754 10

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disease of unknown etiology characterized by metaphyseal dysostosis, unpigmented hair, and defective cellular immunity. We studied peripheral blood mononuclear cells (PBMC) of a boy with CHH and combined immunodeficiency in an attempt to characterize further the immune defect in this disease. Stimulation of his PBMC with mitogens was associated with severely depressed IL-2 and interferon-gamma (IFN-gamma) synthesis and IL-2 receptor alpha-chain (IL-2R alpha) expression and resulted in poor lymphocyte proliferation that was only modestly upregulated by the addition of recombinant IL-2 (rIL-2). The defective proliferation and lymphokine synthesis were not corrected by the addition of phorbol myristate acetate (PMA) and ionomycin, agents that bypass receptor-mediated signalling, indicative of a distal abnormality. Importantly, the levels of mRNA encoding c-myc, IL-2R alpha, IL-2 and IFN-gamma were markedly decreased in patient lymphocytes stimulated with PMA+ionomycin as compared to control lymphocytes. The defect in the expression of these early activation genes was selective in that induction by mitogens of mRNA encoding other early activation gene products such as c-fos and c-jun was not impaired. These results suggest that the underlying defect in this patient and perhaps others with CHH may be an abnormality in a component of intracellular signalling pathways or in a trans-acting factor which regulates the expression of a selected number of early activation genes.
 ...
PMID:Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID). 755 1

Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.
 ...
PMID:Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. 2142 50

Receptors for IgG (Fc gamma R) are expressed by small subpopulations of peripheral blood T lymphocytes. Our studies demonstrate that T lymphocytes can be induced in vitro to express two different low-affinity Fc gamma R. Mitogen activation of peripheral blood T lymphocytes obtained from eight healthy individuals leads to considerable augmentation of the Fc gamma RIII+ (CD32) T cell subpopulation. The highest percentage of CD32 expressing T lymphocytes could be detected after three days of activation. The T cell subpopulation which transiently express the CD32 antigen, encompasses CD4+ and CD8+ cells. Molecular cloning of the CD32 antigen by reverse transcription and polymerase chain reaction demonstrates that activated human T lymphocytes express the Fc gamma RIIIb2 isoform. The percentage of the Fc gamma RIII+ (CD16) T cell subpopulation was significantly increased only in the lymphocyte populations obtained from three out of eight volunteers immediately after mitogen activation. However, during short-term cell culture the CD16 expressing CD8+ T cell subset increased in the T cell population from all individuals investigated. During this time, the IL-2 receptor alpha-chain (CD25) expression level decreased as a function of time. In contrast to the CD8+CD16+ T cells, the percentage of the non-MCH-restricted CD56+CD16+ T cells was not influenced by mitogen activation and time of cell cultivation. We could show that CD16 in T cells is able to mediate a stimulus leading to proliferation of the CD8+CD56-CD16+ T cells but not that of the CD56+CD16+ T cell subset. This discrepancy cannot be explained by the expression of different Fc gamma RIII isoforms, because both T cell subsets express Fc gamma RIIIA alpha, as we demonstrate in this report.
 ...
PMID:Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32) and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes. 764 65

Adult T cell leukemia-derived factor (ADF)/Thioredoxin (TRX), originally defined as an IL-2 receptor alpha-chain/p55 inducer, has many cytokine-like activities. We reported that the release of major basic protein (MBP) from mature eosinophils stimulated with cytochalasin B and C5a were augmented after preincubation with recombinant ADF/TRX. The addition of a TRX specific inhibitor, BE40644, suppressed the augmentation of MBP release from mature eosinophils. It is suggested that BE40644 is applicable in allergic diseases associated with eosinophils.
 ...
PMID:Role of ADF/TRX and its inhibitor on the release of major basic protein from human eosinophils. 765 31


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