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)

A 48-year-old woman was admitted with neck tumors and cutaneous nodules. On the histological basis of the skin nodule biopsy, a metastatic anaplastic carcinoma was suspected. Immunohistochemical studies showed the presence of Ki-1 antigen, IL-2 receptor antigen, leukocyte common antigen (LCA), CD3 and CD4 on the tumor cells compatible with Ki-1 positive anaplastic large-cell lymphoma. This case was, however, finally diagnosed as adult T cell lymphoma (ATL) of a helper/inducer phenotype. She was born in Kagoshima. The serum anti-ATL associated antigen (ATLA) was positive. Southern blot analysis on the DNA extracted from the skin tumor cells showed a monoclonal integration of HTLV-1 proviral DNA. The results suggested that Ki-1 positive lymphomas may include a subset of ATL with a large-cell histology.
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PMID:[Adult T-cell leukemia/lymphoma, histologically presenting Ki-1 positive anaplastic large cell lymphoma]. 133 94

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells. IL-4 and IL-6 increased significantly EBV-B cell proliferation after 3 and 5 days of culture, where IL-2 had no effect. The effect of IL-4 and IL-6 on EBV-B cells was abolished after pre-incubation with anti-IL-4 and anti-IL-6 neutralising antisera, respectively. TPA induced a dose dependent inhibition of proliferation both in serum free and 10% fetal calf serum (FCS) supplemented culture medium. Combinations of TPA and interleukins did not restore lymphoblastoid cell proliferation to background levels. All possible combinations of the three cytokines showed no synergistic or antagonistic effect on proliferation. TPA induced significant phenotypic changes of EBV immortalised B lymphocytes, by increasing IL-2 receptor (IL-2R) expression and decreasing CD20 and CD23 antigen expression. Other B cell differentiation antigens; HLA-DR, CD19, and transferrin receptor (CD71), did not demonstrate significant changes. A dose dependent inhibition of CD21 and increase in CD22 expression was observed in 2 out of 3 lymphoblastoid cell lines tested.
Leuk Lymphoma 1992 Sep
PMID:Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes. 133 96

Three cases of malignant lymphoma were examined immunohistochemically using anti-Leu monoclonal antibodies (MAB) against B lymphocytes, T lymphocytes subsets, NK cells, IL-2 receptor. In all three cases tumor cells were stained with anti-B cell's MABs, that is they were diagnosed as B cell type of malignant lymphoma. Moderate tumor-infiltrating lymphocytes in the parenchyma or around blood vessels were observed, and majority of these cells were T lymphocytes, demonstrating Leu 2a or Leu 3a + 3b positive phenotypes. IL-2 receptor positive cells also found in the parenchyma of these tumors. T lymphocyte subsets, such as Leu 2a positive cells and Leu 3a + 3b positive cells, were analyzed by means of double immunofluorescence staining method using the combination of Leu 2a and Leu15, or Leu 3a + 3b and Leu 8 MABs. This method demonstrated that most of Leu 2a positive cells were negative for Leu 15 and that the majority of Leu 3a + 3b positive cells were negative for Leu 8. These results suggested that tumor-infiltrating lymphocytes in the malignant lymphoma were mainly activated cytotoxic or helper T cells.
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PMID:[Analysis of tumor-infiltrating lymphocyte in primary malignant lymphoma of the central nervous system using double immunofluorescence staining method]. 153 33

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.
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PMID:Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness. 156 2

Activation of resting T-lymphocytes induces synthesis of interleukin-2 (IL-2) and expression of cell surface receptors for this lymphokine. In contrast to resting normal T-cells that do not express high-affinity IL-2 receptors (IL-2R), abnormal T-cells of patients with leukemia-lymphoma, certain autoimmune disorders, and individuals rejecting allografts express this receptor. Exploiting this difference in receptor expression, antibodies to the IL-2 receptor have been used effectively to treat patients with leukemia and lymphoma. One approach is to use monoclonal antibodies produced in mice; the disadvantage is that they are highly immunogenic. In an effort to reduce the immunogenicity of the mouse monoclonal antibodies, monoclonal-antibody-mediated therapy has been revolutionized by generating humanized antibodies produced by genetic engineering in which the molecule is human except for the antigen-combining regions, which are retained from the mouse. Further, to increase its cytotoxic effectiveness, the monoclonal antibody has been armed with toxins or radionuclides. Alternatively, IL-2 itself has been linked to a toxin to kill IL-2 receptor-bearing cells. Thus, IL-2 receptor-directed therapy provides a new method for treating certain neoplastic diseases and autoimmune disorders and for preventing allograft rejection.
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PMID:The multichain interleukin-2 receptor: a target for immunotherapy. 172 19

The aim of the present work was to study regulatory interactions between MHC class I molecules and the interleukin (IL)-2, IL-3, and IL-4 receptors and functional interactions between the receptors for IL-2 and IL-4. Our major observations were: (1) quiescent splenic T cells exposed to specific anti-MHC class I antibodies become responsive to IL-2 and IL-4 stimulation; (2) T-cell clones (CTLL-2 and HT-1) grown at high cell density or low IL-2 concentrations become refractory to IL-2 and IL-4 stimulation. After exposure to anti-class I antibodies the refractory cells recover responsiveness to lymphokine-induced proliferation; (3) IL-2 receptor expression is non-inducible in class I-negative T-lymphoma cells, but is inducible following class I gene transfection of the cells; (4) exposure of T-cells and clones to IL-2 receptor antibody increases the responsiveness to IL-4 stimulation; (5) IL-2 and IL-4 act synergistically at low and substimulatory lymphokine levels; and (6) IL-3 responsiveness of hemopoietic cells is not influenced by exposure to anti-MHC class I antibody. It is concluded that class I molecules are of importance for the functional expression of the receptors for IL-2 and IL-4 and that these receptors are functionally interrelated.
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PMID:T-cell activation. IV. Evidence for a functional linkage between MHC class I, interleukin-2 receptor, and interleukin-4 receptor molecules. 183 52

A continuous cell line was established from the blood of a patient (HH) with an aggressive cutaneous T-cell leukemia/lymphoma who lacked antibodies to human T lymphotrophic virus, type I. The immunophenotype of the cultured cells was CD2+, CD3+, CD4+, CD5+, CD8-, DR+ and CD25- (Tac, IL-2 receptor alpha chain). Southern-blot hybridization analysis of T-cell-receptor beta chain DNA demonstrated the same rearrangement in freshly isolated blood cells and cultured cells, indicating that the cell line was derived from the patient's malignant clone. Since cultured T-cells grew in complete medium without added IL-2, we investigated whether HH cells could be producing and responding to IL-2 in an autocrine fashion. However, no IL-2 was detectable in supernatant from the cell line, while antibodies to IL-2, or to the IL-2 receptor alpha or beta chains did not inhibit cell growth. In addition, no mRNA message for IL-2 was detectable in these cells. The results appear to exclude an autocrine IL-2-dependent mechanism of cell growth for this T-cell line. Although cultured HH cells lacked detectable IL-2 receptor alpha chain, they did show increased proliferation to exogenous IL-2. Binding studies with 125I-IL-2 demonstrated an intermediate affinity receptor for IL-2, KD = 1.7 nM, with 6400 binding sites per cell, suggesting the presence of an IL-2 receptor beta chain. Consistent with these findings 125I-IL-2 cross-linking studies demonstrated a single receptor calculated to be 75 kDa. Also, the beta chain of the IL-2 receptor was detected by immunofluorescence using specific monoclonal antibodies (MAbs). Nanomolar concentrations of an IL-2-diphtheria toxin fusion protein inhibited cellular protein synthesis, an effect abrogated by native IL-2. These findings indicate that the IL-2 receptor beta-chain was functional. This novel mature T-cell line may be useful in studies of IL-2 receptor regulation and in analysis of the mechanism of T-cell leukemogenesis.
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PMID:Establishment of an IL-2 independent, human T-cell line possessing only the p70 IL-2 receptor. 187 69

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.
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PMID:Immunologic markers in non-Hodgkin's lymphoma. 193 59

The present work demonstrates that antibody-induced cross-linking of MHC class I antigens on Jurkat T lymphoma cells leads to a rise in intracellular calcium (Cai2+) and, in the presence of phorbol ester (PMA), to IL-2 production and IL-2 receptor expression. The rise in Cai2+ exhibited a profile very different from that obtained after anti-CD3 antibody-induced activation suggesting that activation signals are transduced differently after binding of anti-CD3 antibody and class I cross-linking, respectively. However, when Cai2+ was examined in individual Jurkat cells by means of a digital image processing system no differences were observed after cross-linking with anti-CD3 and anti-MHC class I antibodies, respectively. Two CD3-negative mutant lymphoma lines were nearly totally refractory to class I cross-linking. Taken together our results may indicate the existence of a functional linkage between the T cell receptor complex and MHC class I molecules.
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PMID:T cell activation. II. Activation of human T lymphoma cells by cross-linking of their MHC class I antigens. 213 76

We report the clinicopathologic findings of 41 patients with Ki-1 (CD30)-positive large cell lymphoma. The median age was 50 years; 13 patients were under 40 years of age. Ten patients presented with extranodal disease. Fifty-five percent of the patients presented with stage I or II disease, and bone marrow involvement was histologically documented in 30% and occurred exclusively in patients over 40 years of age. Two cytomorphologically distinct groups of Ki-1--positive large cell lymphomas could be separated. Group A lymphomas consisted of pleomorphic large cells, sometimes with wreathlike and embryo-like nuclei, whereas group B lymphomas displayed a rather monomorphic appearance. Clinically the two groups of lymphomas differed with respect to stage of disease, frequency of bone marrow involvement, and median survival. On paraffin sections, the Ki-1--related antibody Ber-H2 provided excellent staining results in all cases. Immunologic phenotyping disclosed a T cell type in the majority of cases, revealed marked loss of differentiation antigens, and frequent expression of HLA-DR and IL-2 receptor. The overall median survival was 13 months. Age below 40 years, limited stage of disease (I and II), and, although not statistically significant, lymphoma morphology were associated with longer survival. We conclude, that Ki-1--positive large cell lymphomas represent a morphologically and immunologically heterogeneous category of hematolymphoid neoplasms derived from dedifferentiated and activated lymphoid cells with marked age-dependent prognosis.
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PMID:Ki-1-positive large cell lymphoma. A clinicopathologic study of 41 cases. 184 10


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