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)

Many cytokines have been documented to have a multiplicity of biological effects by acting on a variety of cells. In order to determine whether human BCGF-II acts on any cells in addition to normal B cells, the effect of human BCGF-II on murine thymocytes, human peripheral blood T cells, a human natural killer-like cell line, YT, and Epstein-Barr virus (EBV)-transformed B-cell lines was further examined. BCGF-II augmented incorporation of [3H]thymidine by murine thymocytes in combination with suboptimal doses (0.5 microgram/ml) of concanavalin A (Con A) but not at lower doses (0.1 microgram/ml) of Con A, a concentration usually used for interleukin 1 (IL-1) assays. BCGF-II could not induce proliferation or Tac antigen (Ag) expression on normal peripheral blood T cells stimulated with OKT3 antibody. Both proliferation and Tac Ag expression on YT cells were also augmented by BCGF-II. BCGF-II induced both high- and low-affinity IL-2 receptor (IL-2R) on YT cells as determined by 125I-IL-2-binding assay. Two of seven EBV-transformed B-cell lines tested (ORSON and AUM cells) in response to BCGF-II exhibited augmentation of proliferation and cell surface Tac Ag expression. BCGF-II in the presence of low doses (0.1 microgram/ml) of phorbol myristate acetate (PMA) also induced Tac Ag mRNA (3.5 and 1.5 kb) in these B-cell lines. The IL-2R induced on these B-cell lines, however, consisted mostly of low-affinity receptors. Both Tac Ag and its mRNA in these B-cell lines were not induced by Forskolin but by PMA, suggesting that this induction may involve protein kinase C. The present study shows that human BCGF-II can stimulate YT cells, murine thymocytes, and some EBV-transformed B-cell lines but not peripheral blood T cells. Consequently, BCGF-II can induce the growth and differentiation of a number of cell types in addition to normal B cells.
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PMID:A major 50-kDa human B-cell growth factor-II induces both Tac antigen expression and proliferation by several types of lymphocytes. 282 95

The role of interferon (IFN)-gamma in the activation of human T cells was investigated. Addition of IFN-gamma to mixed-lymphocyte cultures (MLC) augmented both the proliferation and the development of T-cell-mediated cytotoxicity. IFN-gamma also augmented the early expression on CD8+ but not CD4+ lymphocytes of IL-2 receptor alpha chain (Tac antigen) and Class II major histocompatibility antigen (HLA-DR). This effect synergized with that caused by interleukin 2 and was not observed with IFN-alpha. The addition of neutralizing antibody against IFN-gamma to MLC suppressed the development of cytotoxicity and proliferation and the expression of activation antigens on CD8+ cells. In experiments in which highly purified CD8+ T cells were activated with cell-free stimuli, IFN-gamma slightly but significantly augmented proliferation, antibody to IFN-gamma suppressed proliferation, and excess IFN-gamma reversed this suppression. It is concluded that (i) IFN-gamma augmented activation of T cells in human MLC, (ii) IFN-gamma exerted effects directly on T cells, and (iii) IFN-gamma preferentially augmented CD8+ cell activation.
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PMID:Effects of interferon-gamma on the activation of human T lymphocytes. 282 98

Anti-T3-induced T cell activation was standardized in human peripheral blood lymphocytes with respect to dose response, time kinetics and effect of exogenous IL-2 on blastogenesis and on IL-2 receptor expression, identified by anti-Tac monoclonal antibody. IL-2 was able to significantly increase 3H-thymidine uptake and Tac antigen expression in unstimulated and anti-T3 activated lymphocytes. This enhancement was more evident in cultures stimulated with non-mitogenic concentrations of anti-T3, supporting the hypothesis that these concentrations sensitize T cells to the Tac-inducing effects of IL-2. This model of lymphocyte activation was then applied to selected immunocompromized elderly subjects. The aged subjects showed depressed blastogenetic responses and Tac antigen expression, which were not corrected by prolonging the time of cultures. Aged lymphocytes showed a good response to costimulation with anti-T3 and IL-2, suggesting that at least for the anti-T3 activation pathway they are able to respond to IL-2 signals.
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PMID:Interleukin 2 enhancement of anti-T3-induced lymphocyte activation: standardization and use of this model in immunocompromized elderly subjects. 282 27

Activated T cells express at least two affinity classes of interleukin-2 (IL-2) receptors. The number of low-affinity receptors is normally 10-30 times greater than that of the high-affinity receptors. In this report, normal human T cells are used in a cellular system in which the number of low-affinity receptors can be manipulated. The resulting receptor composition, which has been characterized in a previous report, contain such decreased levels of low-affinity IL-2 receptors that almost half of the surface pool of anti-IL-2 receptor antibody (anti-Tac) binding sites is associated with high-affinity receptors. By using such cells the dynamics and functions of high-affinity IL-2 receptors were studied and compared with receptors on a cell population expressing the normal 10-30-fold excess of anti-Tac binding sites over high-affinity IL-2 receptors. The results reveal that the rapid turnover of high-affinity IL-2 receptors is independent of the quantitative level of Tac antigen expression. The rapid kinetic of IL-2 internalization results in a 80-90% reduction of the steady-state levels of high-affinity receptors in the presence of IL-2. Most importantly, by using a cell population that expresses very low levels of Tac antigens, it became evident that IL-2 internalization is associated with an immediate substantial decrease of the surface level of anti-Tac binding sites. The Tac antigen thus appeared to be internalized together with the high-affinity IL-2 receptor complex but nevertheless the normal 10-30-fold excess of Tac antigens, over high-affinity IL-2 receptors, seems not to influence the process of internalization.
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PMID:Analysis of dynamics and functions of high-affinity interleukin-2 receptors. 282 31

The expression of interleukin 2 receptor (IL-2R) on leukemic cells of natural killer (NK) and T cell lineages in two patients with large granular lymphocytic (LGL) leukemia was examined. The p55 Tac IL-2R was not detected by the indirect immunofluorescence method and it did not participate in the IL-2 binding to the surface of these cells. However, these leukemic cells proliferated in a IL-2 dose-dependent manner and expressed p55. A p75 IL-2 receptor (IL-2-R) subunit was detected on the LGL leukemic cells of both NK and T lineages in a crosslink assay. Thus, it is suggested that the primary signal of IL-2 is mediated by the p75 alone. A study of the inhibitions of the proliferative response of LGL leukemia cells by anti-Tac revealed that both p75 and secondarily induced p55 are required for the cell proliferation.
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PMID:The expression of the p75 subunit of interleukin 2 receptor in Tac negative leukemic cells of two patients with large granular lymphocytic leukemia. 283 27

The addition of both live and ultraviolet-inactivated preparations of human T lymphotropic virus type I (HTLV-I) and HIV to cultures of human peripheral lymphocytes impeded the ability of these cells to respond to phytohaemagglutinin (PHA). This inhibition depended on the concentration of the virus and seemed due, in part at least, to interference with the generation of interleukin-2 (IL-2) activity in the PHA-stimulated cultures. However, the addition of exogenous IL-2 did not effectively restore the lymphocyte proliferative responsiveness of cells which had been co-incubated with these human retroviruses. Exposure to the viruses did not affect expression on co-incubated cells of the Tac antigen, an epitope of the IL-2 receptor, as determined by an indirect immunofluorescence assay. These results suggest that one mechanism through which human retroviruses may be able to impede cellular proliferative responsiveness is interference with the ability of target cells to respond to IL-2, even though IL-2 receptors continue to be expressed under the conditions tested.
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PMID:Inhibition of human lymphocyte mitogenesis by human and other retroviruses. Differential effect of interleukin-2 in restoration of responsiveness. 283 64

Human T-cell leukemia/lymphoma virus I (HTLV-I) is known to be associated with adult T-cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in IL-2 production and its receptor (Tac antigen) expression based on the experimental observations of IL-2-dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T-cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of IL-2 to the culture medium. Cell-surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and IL-2 binding assays revealed that one of the ATL cell lines, HPB-ATL-2, expresses only a minimal amount of IL-2 receptor (IL-2-R) on the cell surface and binds less radiolabelled human recombinant IL-2 than the other highly Tac-positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by IL-2, anti-Tac MAb or the tumor-promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no IL-2 activity toward Con-A-stimulated human peripheral blood lymphocytes, and their growth was not affected by additional IL-2 in cultures. IL-2-independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of IL-2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV-I. Trans-activation of the PX40 gene product of HTLV-I for activation of IL-2-R gene might not be coincidentally associated with stimulation for cell proliferation.
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PMID:IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients. 287 15

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 recognized the IL-2 receptor, has been used to purify the receptor. The recognized the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-Kd glycoprotein comprised of 272 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-Kd 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 normal and malignant lymphocytes. 288 69

Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/- SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s-IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL-2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s-IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex-matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture.
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PMID:Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers. 290 Feb 31

The Acquired Immunodeficiency Syndrome (AIDS) is a disease found primarily in homosexual men, consisting of opportunistic infections and tumors, and is due to an acquired T-cell defect. In the present report, we studied various T-cell functions which might serve to distinguish homosexuals with a symptom complex including lymphadenopathy from those with AIDS. T lymphocytes from the lymphadenopathy and AIDS patients had markedly depressed proliferative responses in the autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR) compared to healthy homosexuals or heterosexual controls (P less than 0.001). Since proliferation in the MLR depends upon interleukin 2 (IL-2), a T-cell growth factor, we studied the production of and response to IL-2 in various groups of homosexuals and heterosexual controls. IL-2 production was markedly depressed in the lymphadenopathy and AIDS patients, 1.0 and 0.1 U/ml, respectively, compared to the healthy homosexual or heterosexual controls, both 5.0 U/ml (P less than 0.05 and P less than 0.01, respectively). Although the auto MLR of the lymphadenopathy patients rose to control values with the addition of exogenous IL-2, the auto MLR of the AIDS patients did not (P less than 0.01). This lack of responsiveness to IL-2 in the AIDS group was due to their inability to generate IL-2 receptors as shown by the absence of IL-2 absorption by activated cells and the absence of the Tac antigen (IL-2 receptor) on these same cells. The T4+ and T8+ T-cell subsets from the AIDS patients each demonstrated depressed IL-2 production and responsiveness following activation with autologous cells or mitogen, as well as the absence of Tac antigen. The diminished T-cell proliferation in the auto MLR in the lymphadenopathy group is associated with one defect, low IL-2 production, while the depressed proliferation in the AIDS group is associated with two defects, low IL-2 production and a lack of IL-2 receptor generation. These studies demonstrate that IL-2 receptor generation helps distinguish homosexuals with lymphadenopathy from those with AIDS, and that in addition to T-cell defects in the OKT4+ T-cell subset there are significant abnormalities in the OKT8+ T-cell subset in AIDS patients.
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PMID:Diminished interleukin 2 production and receptor generation characterize the acquired immunodeficiency syndrome. 293 69


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