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)

Co-stimulation of highly purified peripheral T lymphocytes from healthy blood donors with the adhesion molecules CD2 and CD28 in association with recombinant interleukin-7 (rIL-7) induced T-cell proliferation, multiple cytokine secretion and IL-2 receptivity. We demonstrated that rIL-7 is as potent as rIL-2 in inducing the proliferation of unseparated, CD4+ and CD8+ T cells. In contrast to low or undetectable levels of IL-1 alpha, IL-6 and IL-2, high levels of tumour necrosis factor-alpha (TNF-alpha), IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were secreted. Experiments using blocking antibodies suggested a direct mechanism for rIL-7 co-stimulatory effect, although induction of the CD25/IL-2 receptor alpha-chain (CD25/IL-2R alpha) was observed. Monoclonal antibodies (mAb) against the adhesion molecules CD2 and CD28 are likely to mimic the interaction with their respective physiological ligands [lymphocyte function-associated antigen-3 (LFA-3)/CD58, CD59 and CD48 for CD2, B7/BB1 for CD28]. Taken together, these in vitro data suggest that IL-7 could participate in paracrine interactions between T lymphocytes and thymic stromal cells or dendritic cells, via its potent co-stimulatory activity with CD2 and CD28 adhesion molecules.
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PMID:Interleukin-7 is a potent co-stimulus of the adhesion pathway involving CD2 and CD28 molecules. 790 90

Stimulation of primary human T-lymphocytes via CD2 and CD28 adhesion molecules induces a long-lasting proliferation (> 3 weeks). This potent activation does not require accessory cells, such as monocytes, but depends on persistent interleukin 2 (IL-2) secretion and receptivity, which is associated with high and prolonged expression of the inducible CD25/IL-2 receptor alpha (IL-2R alpha) chain gene. The transcription factor NF-kappa B participates in the regulation of both IL-2 and IL-2R alpha genes, as well as multiple cellular genes involved in T-cell proliferation. To evaluate the role of NF-kappa B in human peripheral blood T-lymphocytes, we previously analyzed the activation of NF-kappa B-related complexes in response to CD2+CD28 costimulation. We demonstrated a long-term induction of p50/p65 heterodimer, a putative p65/c-Rel heterodimer, and a constitutive nuclear expression of KBF1/p50 homodimers. As the role of p50 remains unclear, we focused our present study on NF-kappa B1 (p50/p105) gene regulation. Using electrophoretic mobility shift assays and Western and Northern blot analyses, we studied NF-kappa B1 gene expression during T-cell stimulation via CD2+CD28. We observed a transient 4- to 5-fold increase of NF-kappa B1 gene expression at both the mRNA and protein levels, lasting for at least 24 h. p50 DNA-binding activity apparently stays highly controlled when p105 expression is enhanced by a physiological stimulus of peripheral blood T-cells. Partial inhibition of p50 and p105 expression by NF-kappa B1 antisense oligonucleotides significantly reduced T-cell proliferation and CD25/IL-2R alpha cell surface expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of NF-kappa B1 (p50/p105) gene expression in activation of human blood T-lymphocytes via CD2 and CD28 adhesion molecules. 790 83

A role for CD26 surface antigen (Ag) in both CD3- and CD2-mediated T cell activation has been previously demonstrated. To analyze the functional role of CD26 in the CD3- and CD2-induced activation pathways of cord T cells, which represent the most reliable source of Ag-unprimed T cells, we employed a newly developed anti-CD26 monoclonal antibody, termed anti-1F7, anti-CD3 and anti-CD2 in activating T lymphocytes. The results showed that CD26 Ag is expressed on the surface of almost all resting cord T cells and that its fluorescence intensity is enhanced by activation. The binding of anti-1F7 induced a decrease in CD26 membrane expression, with no detectable effect on the surface expression of other cord T cell-related molecules. Moreover, the modulation of CD26 resulted in an increase in anti-CD3-mediated cord T cell activation through an enhancement in intracellular calcium levels, IL-2 receptor expression, and IL-2 synthesis, whereas it had no effect on cord T cell activation induced by anti-CD2 or anti-CD2 plus exogenous IL-2. The fact that the selective involvement of CD26 in the activation pathway triggered by anti-CD3, but not anti-CD2, could be reversed by prior stimulation of cord T cells with anti-CD3 suggests that this functional feature, which resembles that of mature thymocytes, may be linked to the Ag-unprimed cell phenotype of cord T lymphocytes.
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PMID:Activation of cord T lymphocytes. IV. Analysis of surface expression and functional role of 1F7 (CD26) molecule. 790 98

We have investigated several aspects of gamma delta T cells in sheep. gamma delta T cells of sheep express a unique transmembrane protein termed T19 but lack the expression of particular cell-surface molecules such as CD2, CD4 and CD8 which are typically associated with alpha beta T cells. The majority of gamma delta T cells isolated from animals of all ages examined lacked the expression of CD45RA. A faster rate of activation by gamma delta T cells compared to either CD4 or CD8 T cells was seen in the time-course of IL-2 receptor alpha chain (CD25) cell-surface expression. All gamma delta T cells expressed the CD25 protein within 8 hr of activation whereas the majority of CD4 or CD8 T cells did not express CD25 until 24 hr post-concanavalin A (Con A) stimulation. This difference in the rate of expression of activation molecules was not restricted to CD25, as a similar trend was seen with cell-surface expression of major histocompatibility complex (MHC) class II molecules. We have used the distinct phenotypic profile of ovine gamma delta T cells to purify these cells by positive selection via the T19 molecule to assess their in vitro proliferative response to various antigens. Routinely, cell populations comprising more than 93% gamma delta T cells with yields of approximately 55% were obtained. Purified gamma delta T cells were capable of responding to Mycobacterium tuberculosis antigen in a primary and secondary in vitro proliferation assay and to ovalbumin in a secondary response. Ovine gamma delta T cells showed little, if any, proliferative response to allogeneic stimulator cells.
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PMID:Antigen recognition and activation of ovine gamma delta T cells. 792 94

Changes in regulatory T-cell subset (including the recently described CD4 helper inducers or suppressor inducers) balance in the peripheral blood may play a role in the pathogenesis of primary Sjogren's syndrome (SS). Direct immunofluorescence and flow cytometry were used to quantitate and analyse peripheral blood lymphocytes in 15 patients with primary SS and 15 control subjects. A reduction in the percentage of circulating CD4 lymphocytes was observed in patients with SS. There was no quantitative abnormality in the percentage of circulating CD4+ 2H4+ (suppressor inducer), CD4+ 4B4+ (helper inducer), CD2, CD3, CD8, CD8+ 2H4+, CD8+ 4B4+, CD25 (IL-2R), CD19, CD16, CD57 lymphocytes in the patients. Circulating CD8 lymphocytes expressing the activation marker HLA-DR were increased in the patients. The functional status of peripheral blood lymphocytes was assessed by PHA (phytohaemagglutinin) stimulation followed by monitoring their proliferative response by radiolabelled thymidine uptake and expression of CD25 (Interleukin-2 receptor). A reduction in the proliferative response of total, CD4-depleted, and CD8-depleted lymphocytes suspensions to PHA was demonstrated. The level of expression of CD25 (IL-2 receptor) was similar in patients and controls before and after 24 h stimulation with PHA. We conclude that there is a disturbance in the functional properties of peripheral blood T cells that can contribute to the immunopathogenesis of SS. Meanwhile, the quantitative reduction of suppressor/inducer lymphocytes as defined by the CD4 2H4 phenotype can be precluded from a role in the development of such an autoimmune condition.
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PMID:Phenotypic and functional abnormalities in the peripheral blood T-cells of patients with primary Sjogren's syndrome. 808 85

Stimulation of highly purified human T-cells via CD2 and CD28 adhesion molecules induces and maintains proliferation for more than 3 weeks. This potent interleukin 2 (IL-2)-dependent activation does not require monocytes or accessory cells. Long-lasting IL-2 receptivity is associated with high-level expression of the inducible IL-2 receptor alpha chain (IL-2R alpha) gene that is regulated at both transcriptional and posttranscriptional levels. Increase of IL-2R alpha gene transcription involves the enhanced binding of the transcription factor NF-kappa B to its consensus sequence in the 5'-regulatory region of the IL-2R alpha gene. To dissect the molecular basis for the unusually persistent transcription of the IL-2R alpha gene, we analyzed nuclear NF-kappa B binding to a radiolabeled IL-2R alpha kappa B-specific oligonucleotide probe during the time course of CD2 + CD28 activation. Resting T-cell nuclear extracts contained KBF1/p50 homodimer. After stimulation, two new kappa B-specific complexes were identified as NF-kappa B p50-p65 heterodimer and putative c-Rel homodimer or c-Rel-p65 heterodimer. Both inducible complexes persisted for at least 3 weeks. Their relative levels were very similar for the duration of proliferation. In parallel, CD2 + CD28 activation triggered a significant intracellular thiol decrease, suggesting that oxygen radicals are involved in the signaling pathway of adhesion molecules. Finally, micromolar amounts of pyrrolidine dithiocarbamate, an oxygen radical scavenger that efficiently blocked the nuclear appearance of NF-kappa B in T-lymphocytes, also inhibited IL-2 secretion, IL-2R alpha cell surface expression, and T-cell proliferation. Together, these results suggest that NF-kappa B plays an important role in long-term activation of human primary T-lymphocytes via CD2 + CD28.
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PMID:Activation of primary human T-lymphocytes through CD2 plus CD28 adhesion molecules induces long-term nuclear expression of NF-kappa B. 809 18

We have recently shown that a single transfusion of red blood cells to normal human volunteers significantly increases the secretion of a variety of cytokines. In the present study we explored the in vitro effect of whole red blood cells on various T cell and monocytes functions of autologous human or mouse origin. This in vitro model would allow us to further determine in future studies the membranal determinants or the intracellular products of the RBC responsible for the enhancing effect. We demonstrate in this study that addition of autologous erythrocytes to human mononuclear cells or mouse spleen cell cultures results in enhancement of cellular responses to suboptimal concentrations of mitogens. These include cell proliferation, the secretion of IL-2, colony stimulating factor (CSF), interferon-gamma, tumor necrosis factor, and interleukin-6 by human MNC, and cell proliferation, IL-2, IL-3, and CSF by mouse spleen cells. The enhancing effect was dose dependent. Moreover, RBC are shown to directly enhance the expression of IL-2 receptors on both human and mouse cells without the need for the presence of mitogenic stimulation. The expression of IL-2R was measured both by acquisition of responsiveness to exogenous recombinant IL-2 and by immunofluorescence staining. We suggest that whole red blood cells exert a general enhancing effect on the secretion of a variety of cytokines and induce IL-2 receptor expression, probably through nonspecific interaction between membranal domains on erythrocytes and CD2 antigen on T cells.
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PMID:Enhancing effects of autologous erythrocytes on human or mouse cytokine secretion and IL-2R expression. 809 64

The mitogenic activity of human T-cell leukemia virus type I (HTLV-I) is triggering the proliferation of human resting T lymphocytes through the induction of the interleukin-2 (IL-2)/IL-2 receptor autocrine loop. This HTLV-I-induced proliferation was found to be mainly mediated by the CD2 T-cell antigen, which is first expressed on double-negative lymphoid precursors after colonization of the thymus. Thus, immature thymocytes express the CD2 antigen before that of the CD3-TCR complex. We therefore investigated the responsiveness of these CD2+CD3- immature thymocytes and compared it with that of unseparated thymocytes, containing a majority of the CD2+CD3+ mature thymocytes, and that of the CD2-CD3- prothymocytes. Both immature and unseparated thymocytes were incorporating [3H]thymidine in response to the virus, provided that they were cultivated in the presence of submitogenic doses of phytohemagglutinin. In contrast, the prothymocytes did not proliferate. Downmodulation of the CD2 molecule by incubating unseparated and immature thymocytes with a single anti-CD2 monoclonal antibody inhibited the proliferative response to HTLV-I. These results clearly underline that the expression of the CD2 molecule is exclusively required in mediating the proliferative response to the synergistic effect of phytohemagglutinin and HTLV-I. Immature thymocytes treated with a pair of anti-CD2 monoclonal antibodies were shown to proliferate in response to HTLV-I, even in the absence of exogenous IL-2. We further verified that the proliferation of human thymocytes is consecutive to the expression of IL-2 receptors and the synthesis of IL-2. These observations provide evidence that the mitogenic stimulus delivered by HTLV-I is more efficient than that provided by other conventional mitogenic stimuli, which are unable to trigger the synthesis of endogenous IL-2. Collectively, these results show that the mitogenic activity of HTLV-I is able to trigger the proliferation of cells which are at an early stage of T-cell development. They might therefore represent target cells in which HTLV-I infection could favor the initiation of the multistep lymphoproliferative process leading to adult T-cell leukemia.
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PMID:Human T-cell leukemia virus type I-induced proliferation of human immature CD2+CD3- thymocytes. 810 12

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
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PMID:Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. 815 60

Using monoclonal antibodies in immunohistochemistry, the distribution of the cells with the following surface antigens was studied in samples of proximal and distal small intestine of five 6-month-old pigs: CD2, CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T cells), accessory cell marker (monocyte/granulocyte), MHC Class II (DRw), and interleukin 2 (IL-2) receptor. CD2+ cells were found in high numbers in both the epithelium and the lamina propria. More cells were demonstrated in villis than in crypts (proportion approximately 4:1). At least two subpopulations of intraepithelial lymphocytes were identified: apically in the epithelium there were CD2+CD4-CD8- (double negative) cells, whereas cells expressing CD8 marker were concentrated around the basement membrane. CD4+ cells were localized in the lamina propria towards the villus core. Accessory cells were distributed in crypts and the villus base and more cells were found in ileum than in duodenum. In contrast, MHC Class II+ cells were located predominantly in villi, just underneath the basement membrane, forming a sheath of cells between the CD8+ and the CD4+ cells. Cells expressing IL-2 receptor were sparse but widely distributed in both the lamina propria and the epithelium. This organized cell distribution may be related to the physiology of the mucosal immune system in the gut.
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PMID:Immune cell distribution in the small intestine of the pig: immunohistological evidence for an organized compartmentalization in the lamina propria. 834 59


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