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

This study investigates further the inhibitory effects of transforming growth factor-beta (TGF-beta) on human T-lymphocyte responses to mitogenic stimulation. T cells were stimulated either with mitogenic concentrations of PHA or with submitogenic concentrations of Con A followed by the addition of IL-2. DNA synthesis ([3H]thymidine incorporation) in both systems was inhibited by 60-69% in the presence of TGF-beta, with maximal reduction occurring on days 4 and 5 of culture. Cell surface expression of transferrin receptor (TfR) and IL-2 receptor-alpha (p55) were inhibited by 20-80% in the Con A/rIL-2 system and 20-45% in the PHA system in the presence of TGF-beta. In addition, mitogen-induced up-regulation of TfR and IL-2R mRNA levels were inhibited by TGF-beta. Finally, we investigated the effect of TGF-beta on the assembly of clathrin monomers into assembled coated pits and vesicles, and essential step in TfR and IL-2R alpha turnover. Stimulation of T cells using either mitogen system resulted in an increase in the level of assembled clathrin, which was almost completely inhibited by TGF-beta. These findings suggest that TGF-beta may act at several sites in mitogen-mediated proliferative pathways to contribute to the inhibition of T-cell proliferation.
Lymphokine Cytokine Res 1992 Dec
PMID:Transforming growth factor-beta inhibits human T-cell proliferation through multiple targets. 147 83

Interleukin 6 (IL-6) signal is transduced through gp130 that associates with a complex of IL-6 and IL-6 receptor. Truncations or amino acid substitutions offe introduced in the cytoplasmic region of human gp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL-6-mediated growth signal. In the 277-amino acid cytoplasmic region of gp130, a 61-amino acid region proximal to the transmembrane domain was sufficient for generating the growth signal. In this region, two short segments were significantly homologous with other cytokine-receptor family members. One segment is conserved in almost all members of the family, and the other is found especially in granulocyte colony-stimulating factor receptor, interleukin 2 receptor beta chain, erythropoietin receptor, KH97 (a granulocyte/macrophage colony-stimulating factor receptor-associated molecule), and interleukin 3 receptor. gp130 molecules with mutations in either of these two segments could not transduce growth signal. Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation of gp130.
Proc Natl Acad Sci U S A 1991 Dec 15
PMID:Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. 166 92

Erythropoietin (EPO) mediates the growth and differentiation of erythroid progenitors through its interaction with a specific receptor. Using a partial cDNA clone for the murine erythropoietin receptor, we isolated a human genomic clone containing the erythropoietin receptor gene. The coding region of the human EPO receptor gene is contained within eight exons spanning approximately 6 kb. The human gene has a great deal of structural similarity and sequence homology with the murine gene. The murine gene also has eight exons, although the size of each intron is somewhat different. The locations at which the introns interrupt the coding sequence are conserved precisely. The genomic organization of the EPO receptor gene is also shown to be homologous to the genomic organization of the IL-2 receptor beta chain gene. The sequence of 1.1 kb of 5' flanking DNA was characterized and contains consensus sequences for both Sp1 and GATA-1 binding sites and an initiator (Inr)-like element, but lacks both a canonical TATA box and the CACCC consensus sequence found in the murine gene.
Genomics 1991 Dec
PMID:Genomic organization of the human erythropoietin receptor gene. 166 13

B-cells extracted from periodontal disease tissue were analyzed for the presence of activation markers using a range of monoclonal antibodies. In adult periodontitis (AP), 6% of B-cells expressed the IL-2 receptor (CD25) compared with 1-2% in peripheral blood and healthy or marginal gingivitis (H/MG) gingival B-cells. There was also an increase in the mean percentage of IgD-positive B-cells and a decrease in CD21 and CD22 expression. In both AP and H/MG lesions, 20-22% of the B-cells expressed CD23 compared with less than 5% in peripheral blood. As B-cells are activated by day 3 in culture and start differentiating into immunoglobulin-secreting cells by day 6, B-cell phenotypes were assayed at these times in this study. Following stimulation with the periodontopathic bacterium Porphyromonas gingivalis, the expression of CD23, CD21 and CD22 on B-cells extracted from AP lesions remained relatively constant over the 6-d culture period. However, with Fusobacterium nucleatum stimulation, there was a significant decrease in CD23, CD21 and CD22 expression after 3 d in culture, which corresponds to the activation time for B-cells. These results show that B-cells extracted from periodontal disease tissue display a range of activation markers and on stimulation, demonstrate differing responses to individual periodontopathic bacteria.
Oral Microbiol Immunol 1991 Dec
PMID:Phenotypic analysis of B-cells extracted from human periodontal disease tissue. 166 49

Differential expression of various isoforms of leukocyte common antigen (CD45), which arises from alternate mRNA splicing, identifies naive and memory populations of human T cells. Some memory (CD45RO+ CD45RA-) populations of CD4+ T cells from adult individuals express IL-2 receptor (IL-2R) alpha-chain (CD25), but naive (CD45RO- CD45RA+) CD4+ T cells only do so to a small degree. We found that a small but significant fraction of CD4+ T cells in neonatal blood expressed CD25, although most generally exhibited the phenotype of naive cells. It was demonstrated that purified neonatal CD25+ CD4+ T cells expressed mRNA for the IL-2R alpha-chain. Two-color immunofluorescence analysis disclosed that a CD25+ population of neonatal CD4+ T cells had the naive (CD45RA+ CD45RO-) phenotypes. These CD25+ CD4+ T cells from newborns could express mRNA for some specified lymphokines such as IL-4, IL-5, and interferon-gamma on activation in a similar manner to CD45RO+ (memory) CD4+ T cells from adults. Notably, polymerase chain reaction analysis demonstrated that neonatal CD45RA+ CD4+ T cells expressing CD25 contained spliced mRNA transcripts possibly encoding CD45RO in addition to CD45RA-associated transcripts, seemingly indicating that this population might be in the recently antigen-primed states. Such a small population of CD45RA+ CD4+ T cells expressing CD25 appeared to be present in the blood throughout human life. The results suggest that CD4+ T cells with the naive (CD45RA+) phenotype expressing IL-2R alpha-chain (CD25) represent the novel transitional population in the maturation process of naive into memory CD4+ T cells.
Int Immunol 1991 Dec
PMID:A novel subpopulation of CD45RA+ CD4+ T cells expressing IL-2 receptor alpha-chain (CD25) and having a functionally transitional nature into memory cells. 168 71

Using the mouse interleukin 3 (IL-3) receptor cDNA as a probe, we obtained a homologous cDNA (KH97) from a cDNA library of a human hemopoietic cell line, TF-1. The protein encoded by the KH97 cDNA has 56% amino acid sequence identity with the mouse IL-3 receptor and retains features common to the family of cytokine receptors. Fibroblasts transfected with the KH97 cDNA expressed a protein of 120 kDa but did not bind any human cytokines, including IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, cotransfection of cDNAs for KH97 and the low-affinity human GM-CSF receptor in fibroblasts resulted in formation of a high-affinity receptor for GM-CSF. The dissociation rate of GM-CSF from the reconstituted high-affinity receptor was slower than that from the low-affinity site, whereas the association rate was unchanged. Cross-linking of 125I-labeled GM-CSF to fibroblasts cotransfected with both cDNAs revealed the same cross-linking patterns as in TF-1 cells--i.e., two major proteins of 80 and 120 kDa which correspond to the low-affinity GM-CSF receptor and the KH97 protein, respectively. These results indicate that the high-affinity GM-CSF receptor is composed of at least two components in a manner analogous to the IL-2 receptor. We therefore propose to designate the low-affinity GM-CSF receptor and the KH97 protein as the alpha and beta subunits of the GM-CSF receptor, respectively.
Proc Natl Acad Sci U S A 1990 Dec
PMID:Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. 170 17

Peripheral blood lymphocytes from 47 Hispanic poly-drug users with a history of cocaine abuse were analyzed for in vitro production of interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-interferon (IFN) and plasma levels of soluble IL-2 receptor (SIL-2R). Cocaine use was confirmed and quantified by analysis of hair and urine samples, and subjects were grouped into 3 based on the extent of cocaine metabolites detected. No significant differences in IL-1 and IFN production were seen between the 3 groups. However, subjects with higher levels of cocaine in hair also showed higher levels of IL-2. In addition, a positive correlation was seen between cocaine concentrations and IL-2 levels. A corresponding negative correlation was seen between cocaine levels and levels of plasma SIL-2R. These findings suggest modulation of the IL-2 network by cocaine in poly-drug users.
Toxicol Lett 1991 Dec
PMID:Cocaine immunotoxicity: abnormal cytokine production in Hispanic drug users. 172 32

The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of HLA-DR+ T4 L-BAL, and sIL-2R production is independent of the percentage of IL-2+ L-BAL. Our data indicate that the L-BAL activation markers and the functional activity of T-cells represent independent phenomena.
Am Rev Respir Dis 1991 Dec
PMID:Correlation of clinical and immunologic parameters of the inflammatory activity of pulmonary sarcoidosis. 174 45

Metabolic derivatives of arachidonic acid such as prostaglandins and leukotrienes may alter immune responses. Enisoprost (ENO), a synthetic prostaglandin E analog, inhibited the response of human peripheral blood mononuclear cells to phytohemagglutinin in a concentration-dependent fashion: .1, 1.0, and 10 micrograms/ml yielding 4.0, 21.7, and 74.3% inhibition, respectively. ENO also potently inhibited both IL-2 production (measured by ELISA) and IL-2 responsiveness (measured by CTLL-2 response to IL-2) in a concentration-dependent manner, yet did not inhibit acquisition of IL-2 receptors. ENO similarly diminished efferent immune function in a concentration-dependent fashion, as measured by inhibition of cytotoxic T cell and natural killer effector function. A 5-lipoxygenase inhibitor (5-LO), SC-45662, also inhibited mononuclear cell response to PHA in a concentration-dependent manner: 0.1, 1.0, and 10 micrograms/ml yielding 5.0, 9.7, and 79.7% inhibition, respectively. Although 5-LO potently inhibited IL-2 production, it had no effect on IL-2 responsiveness or IL-2 receptor acquisition. Like ENO, 5-LO impaired CTL and NK effector function yet was not as potent in inhibiting CTL effector function. In summary, ENO and 5-LO inhibit afferent and efferent immune function. The inhibitory effects of these drugs are not related to cytotoxicity as cell viability is maintained for 72 hr in the presence of these drugs, and the inhibitory effect is reversible when the drugs are removed. The 5-LO does not inhibit mononuclear cell responses simply by shunting the formation of arachidonic acid precursors to form inhibitory prostaglandins, since it does not impair IL-2 responsiveness in a manner similar to ENO. These two compounds may prove to have clinical utility in organ transplantation if safely achieved serum concentrations of these drugs yield in vivo immunosuppression parallel to our in vitro results.
Transplantation 1991 Dec
PMID:The immunosuppressive properties of enisoprost and a 5-lipoxygenase inhibitor (SC-45662). 175 68

Lymphocyte clones were isolated from CD4+ peripheral-blood lymphocytes (PBL) of melanoma (Me) patient 9923 (HLA-DR7, DQw2, w6), co-cultured for 30 days with autologous accessory cells, allogeneic Me (Me 1811) (HLA-DR7, DQw1, w2), IL-1 beta (2 U/ml) and IL-2 (15 IU/ml). The 55 clones tested displayed a CD3+, CD4+, CD8-, T-cell receptor (TCR) alpha/beta+, gamma/delta- phenotype. Twenty clones were assayed for proliferation in the presence of Me 1811 and B-lymphoblastoid cell line (LCL) 1811, both expressing HLA-class-I and -II (DR7 and DQw2 shared with patient 9923), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-3 (LFA-3) molecules. Eight clones were found to be reactive to Me 1811 but not to LCL 1811. Specificity analysis of these 8 clones revealed that each of them proliferated only to Me 1811, not to other 14 Me and 12 different LCL, suggesting recognition of melanoma-associated antigen (MAA) expressed on the stimulating Me. One clone (103) was analyzed in more detail. A wider specificity analysis showed that it reacted to Me 1811 but not to 10 other Me expressing or not HLA-DR7, 5 normal melanocyte cultures (2 of them typing HLA-DR7-positive when exposed to interferon-gamma--IFN-gamma), 4 tumors other than Me and 20 different LCL. Clones did not show proliferation in the presence of autologous Me cells. Clone proliferation in response to Me 1811 was significantly inhibited by monoclonal antibodies (MAbs) directed to CD3, TCR alpha/beta, TCR beta chain V12, CD4 and HLA-DR. Moreover, following stimulation with Me 1811, clone 103 showed increased surface expression of CD25 (IL-2 receptor) and CD71 (transferrin receptor) and produced significant amounts of IL-2 and IFN-gamma. The supernatant taken from co-culture of clone 103 with Me 1811 augmented the cytotoxicity of PBL 9923 and other allogeneic PBL against K562 and Me 1811. Thus, the lymphocyte clone 103 is a CD4+ Th clone which uses its CD3/TCR alpha/beta complex to recognize an MAA in conjunction with HLA-DR7. Availability of this type of reagent may prove useful to identify and characterize MAA recognized by T lymphocytes.
Int J Cancer 1991 Dec 02
PMID:Human allogeneic melanoma-reactive T-helper lymphocyte clones: functional analysis of lymphocyte-melanoma interactions. 183 14


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