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)

In the burn patient, the mechanisms leading to impaired T lymphocyte activity are unclear. The capacity for T cell proliferation and the expression of Tac antigen (IL-2 receptor) was assessed during the post-burn period in patients with injuries ranging from 5-68% total body surface area. T cell-dependent (polyclonal) immunoglobulin synthesis, mixed lymphocyte reaction and Interleukin-2 production were also determined in these patients and correlated with survival. Surviving patients demonstrated a transient reduction while terminal patients exhibited a permanent reduction in the number of Tac (+) lymphocytes, unrelated to the absolute number of T cells, during the post-burn period. The reduced percentage of IL-2 receptor-expressing T cells coincided with the suppressed antibody response and reduced alloreactivity. Although the concentration of IL-2 was decreased in all patients throughout the hospitalization period, surviving patients showed a gradual increase in its production while terminal patients gradually decreased to undetectable levels. Exogenous recombinant IL-2 induced a significant enhancement of in-vitro polyclonal immunoglobulin production and blastogenesis in the mixed lymphocyte reaction in immunosuppressed patients who demonstrated up to 50% reduction in the percentage of IL-2 receptor positive cells. Thus, the reduced capacity for production of and response to IL-2 after thermal injury may lead to the immunosuppression due to a lack of T lymphocyte clonal expansion. The permanent nature of this defect in patients who died from fatal sepsis may suggest a causative relationship.
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PMID:Impairment of T cell activation in burn patients: a possible mechanism of thermal injury-induced immunosuppression. 294 98

In the present study, we examined the expression of interleukin 2 (IL-2) receptors on normal human B cells as well as established B cell lines. Anti-Tac monoclonal antibody did not bind to freshly separated normal human B cells. Unexpectedly, with the appropriate activation of the normal B cells by anti-mu antibody, phorbol myristate acetate, or Staphylococcus aureus Cowan I (SAC), Tac antigen was induced on the activated B cells. Anti-Tac antibody showed consistent reactivity with two B cell lines that were infected by human T cell leukemia virus (HTLV) and some reactivity with two out of eight Epstein-Barr virus-transformed B cell lines established from normal adult donors. Immunoprecipitation analysis revealed that antigens of similar size with a molecular weight of 50,000-60,000 can be precipitated with anti-Tac antibody from phytohemagglutinin-stimulated normal T cell blasts and normal activated B cells, as well as a cloned B cell line. Binding assays of IL-2 on normal activated B cells and on the cloned B cell (HS1) revealed that B cells have significantly fewer sites and lower-affinity IL-2 receptors compared with phytohemagglutinin-stimulated normal T cell blasts. Finally, biological properties of the IL-2 receptor on B cells were examined by incubating B cells with recombinant IL-2. It was found that moderate concentrations of IL-2 induce significant enhancement of proliferation and differentiation in SAC-activated normal B cells. These results suggest that normal B cells may express functional IL-2 receptors or closely related proteins and thus IL-2 may play a significant role in the modulation of B cell function.
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PMID:Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function. 298 52

The cell surface density of high-affinity membrane receptors for the T-lymphocytotrophic hormone interleukin 2 (IL-2) determines the rate of T-cell-cycle progression. Since 10-fold greater numbers of IL-2 receptor molecules were found by using a radiolabeled monoclonal antibody reactive with IL-2 receptors (anti-Tac) compared with binding of IL-2, the functional relationship of the binding sites recognized by both of these ligands was assessed. In the presence of cycloheximide, IL-2 binding sites declined with a half-time (t1/2) of 2.6 hr, whereas the decay of anti-Tac binding sites was much slower (t 1/2 = 6.4 hr). Moreover, after limited membrane proteolysis, the half-time for the reappearance of IL-2 binding sites was remarkably similar to its decay (t 1/2 = 2.2 hr), while Tac antigen reappearance was markedly retarded, returning to only 20% of original levels within 5 hr after proteolysis. Addition of homogeneous immunoaffinity-purified IL-2 to cell populations that expressed equivalent IL-2 and anti-Tac binding sites resulted in a time- and temperature-dependent 8- to 10-fold enhancement of Tac epitope expression and, simultaneously, a 20-30% diminishment of detectable high-affinity IL-2 binding sites. As the magnitude of the IL-2-dependent proliferative response correlated with the density of high-affinity IL-2 binding sites, rather than Tac antigen levels, quantitation of Tac epitope density does not provide a reliable indication of IL-2-responsiveness among activated T-cell populations. Instead, IL-2-receptor interactions actually promote the loss of IL-2 responsiveness by diminishing the density of high-affinity binding sites at the time that Tac antigen levels are increased.
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PMID:Interleukin 2 regulates its own receptors. 298 18

Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors, but receptors are rapidly expressed on T-cells following interaction of antigens, mitogens, or monoclonal antibodies with the antigen-specific T-cell receptor complex. Using anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified and shown to be a Mr 33,000 peptide that is posttranslationally glycosylated to a Mr 55,000 mature form. Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen. In human T-cell lymphotropic virus-I infected cells, the Mr 42,000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription, thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells. The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells. Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac. One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor.
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PMID:Interleukin 2 receptor (Tac antigen) expression in HTLV-I-associated adult T-cell leukemia. 299 Jun 87

We studied the expression of the interleukin-2 (IL-2) receptor and the proliferative response to exogenous IL-2 of peripheral blood leukemic cells from patients with adult T cell leukemia (ATL) in order to see whether IL-2 receptor expressed on ATL cells is different from normal IL-2 receptor and whether it plays a role in the neoplastic growth in ATL. Peripheral blood leukemic cells from 42 patients with ATL examined expressed IL-2 receptors that were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after the culture for 24 or 48 h. The number of anti-Tac binding sites ranged from 3,100 to 11,400 in fresh cells and from 3,600 to 96,000/cell in short-term cultured leukemic cells, whereas phytohemagglutinin-P (PHA-P)-stimulated normal T cells exhibited 6,900-35,000 anti-Tac binding sites per cell. ATL-derived and human T cell leukemia/lymphoma virus, type I (HTLV-I)-infected cell lines such as MT-1 and Hut102 expressed a much higher number of anti-Tac binding sites. Leukemic cells from 15 patients with ATL examined showed no or very poor proliferative response to various concentrations of immunoaffinity-purified IL-2, although they expressed Tac antigen (Ag). Radiolabeled IL-2 binding experiments demonstrated that ATL leukemic cells could bind IL-2, and they expressed both high and low affinity IL-2 receptors, although the number of high affinity IL-2 receptor was much less than that of low affinity IL-2 receptor and that of anti-Tac binding sites. In contrast, leukemic T cells from a patient with T cell chronic lymphocytic leukemia (CLL), in whom HTLV-I infection was not demonstrated, responded as well as PHA-P-stimulated normal T cells, and their IL-2 receptors, unlike ATL cells, were modulated (down regulated) by anti-Tac antibody. No differences were noted between ATL cells and normal activated T cells in one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the IL-2 receptor. Thus, leukemic cells in ATL spontaneously and continuously express IL-2 receptor, which appears to be abnormally regulated and unresponsive to IL-2. These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells.
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PMID:Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells. 299 59

Because the expression of interleukin 2 (IL-2) receptor and transferrin receptor is essential for the proliferation of T cells to mitogens and antigens, we examined the expression of monoclonal antibody defined IL-2 receptor (Tac antigen) and transferrin receptor on unstimulated as well as on phytohemagglutinin (PHA)-activated highly enriched T cells from patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). A trend of increased proportion of unstimulated T cells with Tac antigen and transferrin receptor was observed in patients with AIDS and ARC when compared to healthy heterosexual controls, but the differences were not significantly (P greater than 0.1). The proportions of Tac+ PHA-activated T cells were, however, significantly decreased in AIDS (P less than 0.001). ARC (P less than 0.001), and asymptomatic homosexuals (P less than 0.01) when compared to healthy heterosexuals. The proportions of transferrin receptor positive PHA-activated T cells were not significantly different among various groups. A significantly (P less than 0.01) decreased production of IL-2 was observed in AIDS. This study suggests that the poor proliferative responses of T cells may be due to several defects in lymphocyte-cytokine cascade and the deficiency of Tac antigen expression and of the production of IL-2 could be a few of several abnormalities contributing to poor T-cell functions in AIDS.
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PMID:Study of activated T cells in man. II. Interleukin 2 receptor and transferrin receptor expression on T cells and production of interleukin 2 in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. 300 Jun 65

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.
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PMID:Systemic lupus erythematosus sera antilymphocyte reactivity: detection of antibodies to Tac-antigen positive T cell lines. 300 53

Interleukin-2 (IL-2) is a lymphokine synthesized by T cells following activation. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells following interaction of the antigen-specific T-cell-receptor complex with appropriately processed and presented antigens. Anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-kDa glycoprotein comprised of 251 amino acids including a single 19-amino transmembrane domain and a short intracytoplasmic domain composed of 13 amino acids at the carboxy terminus. Normal resting T cells and most leukemic T-cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen. In HTLV-I-infected cells, the 42-kDa long open reading frame (tat) protein encoded in part by the tat region of HTLV-I may act as a transacting activator that induces transcription of the IL-2-receptor gene, thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2-receptor expression. The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T cells. Patients with the Tac-positive ATL are being treated with both unmodified and toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
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PMID:The interleukin-2 receptor on malignant cells: a target for diagnosis and therapy. 301 74

Recent studies have demonstrated efficacy of immunotherapies including interleukin-2 (IL-2) in the treatment of malignancies in rodents and humans. High levels of IL-2 receptor-positive cells were found in the peripheral blood of patients receiving recombinant IL-2 in these Phase I clinical trials. This was demonstrated both in patients receiving i.v. IL-2 who had detectable circulating levels of IL-2 as well as in patients receiving i.p. IL-2 who did not. Up to 100% of the anti-Tac binding could be inhibited by preincubation with IL-2 indicating that this was indeed an IL-2 receptor that was identified. Two-color experiments demonstrated that few Leu 2-positive cells (less than 5-10%) but over 30% of the Leu 3-positive cells bore Tac antigen. Most of the M3-positive monocytes were Tac positive (83.7%) and negative for other T-cell (Leu-4) and nonspecific murine markers (Lyt-2 and Thy 1.2). Although normal individuals had a mean of only 186 units/ml (range, 83-335 units/ml) of soluble IL-2 receptor, patients receiving IL-2 had as much as 20,000 units/ml of soluble IL-2 receptor line in their serum. The physiological role of the IL-2 receptor identified on the cell surface of Leu 3 and M3-positive cells as well as in the serum is unclear. Soluble IL-2 receptors appeared in the circulation early following IL-2 administration, approximately 1 week prior to the detection of circulating IL-2 receptor-bearing cells. Further studies will be needed to assess the role of IL-2 in monocyte function, the precise function of IL-2 receptor-bearing Leu 3-positive cells, and the relationship of these findings to the toxicity and success of this immunotherapy in humans.
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PMID:In vivo administration of purified human interleukin-2 to patients with cancer: development of interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors following interleukin-2 administration. 303 May 46

Interleukin 2(IL-2), a lymphokine that is produced by helper T cells, plays a key role in the proliferation of T lymphocytes by interacting with a specific cell surface receptor. Recent studies demonstrated that the IL-2 receptor exists in two forms having different affinities to the ligand and the growth signal seems to be delivered by IL-2 bound to the high affinity, but not the low affinity, receptor. In man, both forms of the IL-2 receptor can be recognized by a monoclonal antibody, anti-Tac. Using this antibody, a cDNA that encodes Tac antigen has been cloned from ATL-derived T cell line. Transfection of the cloned cDNA into mammalian non-T cells, however, resulted in the expression of only a non-functional, low affinity IL-2 receptor. This observation raised a question whether or not the cloned cDNA for Tac antigen actually encodes the functional, high affinity IL-2 receptor. In order to clarify this problem, Tac antigen cDNA was obtained from human PBL cDNA library. This cDNA was connected to RSV-LTR and was transfected into mouse thymoma derived T-cell line EL4, and L929 fibroblast. Then transformants that constitutively express Tac antigen were established. IL-2 binding assay demonstrated that EL4 transformants expressed high affinity as well as low affinity human IL-2 receptor. In contrast, L929 transformants expressed only a low affinity receptor. The growth of the EL4 transformants harboring the high affinity human IL-2 receptor was inhibited by virtue of the specific interaction of the receptor with human, but not mouse, recombinant IL-2. These results demonstrate: the cloned cDNA dose encode a functional IL-2 receptor, the affinity of the IL-2 receptor is variably modified by post-translational events and 3. IL-2/receptor interaction leads to the reversal of the cell growth in EL4 cells. The reconstitution system described here will be of great use in elucidating the mechanism of T cell growth.
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PMID:[Expression of functional human interleukin 2 receptor in mouse cells by using gene transfection]. 309 55


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