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)

Tac antigen, the receptor for human interleukin 2 (IL-2), contains in its intracytoplasmic region a serine residue (Ser-247) that is seemingly the predominant site of protein kinase C-mediated phosphorylation. A number of studies on growth factor receptors have suggested the importance of phosphorylation in receptor structure, function, and regulation. In this study, we generated site-directed mutations in the Tac antigen cDNA to generate mutant receptors in which Ser-247 or Thr-250, a probable site of minor phosphorylation, was replaced with another amino acid that is not accessible to phosphorylation. Study of the expression of these mutant genes in a T-lymphoid cell line has provided no evidence as to the essential role of the above-mentioned residues in determining the degree of receptor affinity, its ability for signal transduction, and phorbol ester-mediated regulation of the receptor. Our results strongly suggest the existence of an IL-2 receptor "complex" in which the Tac antigen is associated with another molecule(s) that is involved in receptor structure, function, and regulation.
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PMID:Intracytoplasmic phosphorylation sites of Tac antigen (p55) are not essential for the conformation, function, and regulation of the human interleukin 2 receptor. 309 87

Interleukin-2 (IL-2) receptor expression is a feature of T-cell activation and T-cell neoplasia. Expression of the IL-2 receptor in human lymphoid lesions was studied in a series of 166 immunophenotyped cases, including nodal and extranodal reactive lymphoid proliferations (44 cases), low-grade B-cell lymphomas (27 cases), intermediate and high grade B cell lymphomas (42 cases), peripheral T-cell lymphomas (13 cases), Hodgkin's disease (12 cases), histiocytic proliferations (15 cases), nonhematopoietic tumors (16 cases), and miscellaneous lesions (7 cases). Low levels of receptor expression were seen in reactive lymphoid lesions, low-grade B-cell lymphomas, and nonhematopoietic tumors (20%, 7%, and 25% of cases, respectively, with greater than 10% positive cells). High levels of receptor expression were seen in cases of peripheral T-cell lymphoma and histiocytic proliferations (86% and 100% of cases, respectively, with greater than 10% positive cells). Intermediate levels of expression were seen in Hodgkin's disease (including Reed-Sternberg cells) and some cases of intermediate and high-grade B-cell lymphomas (58% and 50% of cases, respectively, with greater than 10% positive cells). IL-2 receptor expression is not confined to T-cell neoplasia, but is also a feature of neoplastic and nonneoplastic histiocytic proliferations, Hodgkin's disease, and some intermediate and high-grade B-cell lymphomas. Biologic and therapeutic implications are discussed.
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PMID:IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases. 310 54

Three Hodgkin-derived cell lines (L428, L540, and CO) were studied for rearrangements and expression of immunoglobulin and T-cell receptor genes, and their genotype was compared to the phenotype. As far as the genotype is concerned, all 3 cell lines have characteristics of lymphoid cells; L428 of B, and L540 and CO of T-cell origin. L428 cells have one Ig heavy chain allele rearranged to C gamma and transcribed into RNA, while the second is deleted. Furthermore, L428 cells show an unusual immunoglobulin kappa light chain gene rearrangement involving deletion of the kappa constant gene in one allele, while the remaining kappa and lambda loci are in germline configuration. L540 and CO have, in contrast to L428 cells, the immunoglobulin genes in germline and T-cell receptor genes rearranged. The T-cell receptor beta and gamma genes are rearranged in both L540 and CO, whereas a rearrangement in the alpha locus was detected in L540 cells only. RNA of the size of functional beta chain transcripts was found in CO cells and of the size of functional alpha chain transcripts in L540 cells. All 3 cell lines are classified as immature lymphoid cells with respect to the limited expression of B- and T-cell antigens, respectively, and to the incomplete expression of their antigen receptor. The immaturity of lymphoid differentiation contrasts with the expression of activation antigens, i.e. Ki-1, Ki-24, HLA-DR, and IL-2 receptor. The immaturity of the cells excludes the possibility that the cells were activated along the physiological pathway, i.e. by interaction of the cell with antigen. The results obtained on the cell lines are in accordance with in vivo studies and suggest that Hodgkin and Sternberg-Reed cells are immature lymphoid cells which are activated by a still unknown mechanism.
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PMID:Phenotype versus immunoglobulin and T-cell receptor genotype of Hodgkin-derived cell lines: activation of immature lymphoid cells in Hodgkin's disease. 311 32

Peripheral blood mononuclear cells (PBMC) of normal individuals were found to contain a proportion (4-9%) of in vivo activated lymphoid cells (IVALC). These IVALC were characterized by their expression of interleukin 2 (IL-2) receptors, and by the ability to proliferate in the presence of exogenous IL-2. There was a good correlation between the proportion of IVALC in different cell populations and the level of cell proliferation to IL-2. It was found that IVALC isolated from autologous PBMC of Bacillus Calmette-Guerin (BCG)-immunized individuals contained no significant proportion of purified protein derivative (PPD)-reactive lymphocytes. The addition of IVALC markedly enhanced proliferative responses of the autologous T4+T8-IL-2 receptor-negative cell cultures to antigen stimulation. An increased proportion of activated (IL-2 receptor-positive) lymphocytes was generated in PBMC as compared to autologous T4+T8-IL-2 receptor negative cell cultures after stimulation with PPD. Limiting dilution analysis showed that IL-2 responsive IVALC through expansion markedly affected the cloning efficiency of antigen-proliferating T cells of autologous PPD-stimulated PBMC cultures. Only 1 out of every 11-25 blast cells generated in the PBMC cultures could establish itself as a growing colony based on determinations in six BCG-positive individuals. By using a T4+T8- population depleted of IVALC to generate PPD-reactive lymphocytes, a three- to four-fold increase in the cloning efficiency of antigen-specific cells was obtained.
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PMID:In vivo activated lymphoid cells (IVALC) affect the cloning efficiency of human T lymphocytes reactive to a soluble antigen, purified protein derivative. 312 12

Results of recent studies indicated that a monoclonal ART18 antibody recognizes the receptor sites or closely related structures for IL-2 on activated rat T-cells. The major histocompatibility complex (MHC) class II (Ia) antigens (RT1B and RT1D in rat), detected with OX6 antibody, and OX17 antibody, may be present on activated rat T-cells. In the present report, we examined the effect of corticosteroids and cyclosporine (CsA) on the expression of IL-2 receptors and Ia antigens by the T-cells, which constituted the major cellular component of the ocular infiltration during the period of peak ocular inflammatory activity in experimental autoimmune uveoretinitis (EAU). Lewis rats immunized with retinal S-antigen (S-Ag) and treated for a limited time with suboptimal doses of either CsA or Dexamethasone (Dex) subsequently developed EAU. The inflamed ocular tissues were studied using an immunoperoxidase staining technique. CsA treatment resulted not only in the inhibition of IL-2 receptors on T-cells, but also in the prevention of the induction of Ia antigen expression on T-cells and other non-lymphoid cells. Dex treatment resulted in less inhibition of the expression of both class II antigens and IL-2 receptor by the infiltrating T-cells.
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PMID:Cyclosporine and dexamethasone inhibit T-lymphocyte MHC class II antigens and IL-2 receptor expression in experimental autoimmune uveitis. 312 80

The contribution of interleukin-2 (IL-2)-responsive bystander cells to the proliferative responses of human peripheral blood T lymphocytes to antigens used for sensitization such as Purified Protein Derivative (PPD), Tetanus toxoid (T T) and Influenza virus was investigated. Marked proliferation of the unfractionated peripheral blood mononuclear cells (PBMC) was observed following stimulation with these antigens to which the individuals were known to have been sensitized previously. Depletion of large granular lymphocytes (LGL) from PBMC resulted in substantial reduction in the response of the lymphoid cells in proliferating to the antigens. Proliferation of the T4+T8- (helper)-enriched population, or T4+T8- subset depleted of any IL-2 receptor (IL-2R)-bearing lymphoid cells to these antigens was comparable to that of LGL-depleted PBMC cultures. Cell titration experiments of the blast cells generated from these cultures revealed that PBMC-derived population contained fewer antigen-reactive lymphocytes. These results, therefore, suggested that IL-2-responsive LGL through expansion affected the concentration of antigen-proliferating T cells in the antigen-stimulated PBMC cultures.
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PMID:Analysis of human peripheral blood T lymphocytes proliferating in response to sensitizing antigens: effect of interleukin-2 (IL-2)-responsive bystander cells. 313

Three Hodgkin's disease-derived cell lines were analysed for the organization of immunoglobulin and T cell receptor genes, for the expression of the interleukin 2 (IL-2) receptor gene, and for the cellular oncogene c-myc. All three cell lines have characteristic genotypic markers of lymphoid cells and can be classified as immature lymphoid cells with respect to the incomplete expression of their antigen receptor genes. This immature genotype is in contrast to the expression of activation antigens Ki-1 (CD 30), IL-2 receptor (CD 25), and HLA-DR. The results obtained are in agreement with studies obtained from primary Hodgkin's lymphomas, which are activated by as yet unknown mechanisms.
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PMID:Molecular analysis of Hodgkin's disease-derived cell lines. 313 69

We prospectively evaluated responses to recall antigen in ten cancer patients undergoing immunotherapy and correlated these responses with in vitro proliferation data. Before therapy, eight of ten patients responded normally to at least two of seven antigens of a multitest system (greater than or equal to 2 mm induration at 48 hours), with a mean induration score of 17.9 +/- 4.4 mm and 2.7 +/- 0.5 positive responses per patient. This decreased to 5.9 +/- 2.7 mm (P = .01) and 1.2 +/- 0.5 responses (P = .03) after a week of interleukin-2 (IL-2) therapy, and further to 0.7 +/- 0.7 mm and 0.1 +/- 0.1 positive responses during a second week of therapy consisting of IL-2 plus activated autologous lymphocytes (P less than .01). The in vitro proliferation indices for lymphocytes obtained before skin test application were significantly less after IL-2 compared with pretreatment for concanavalin A ([con-A] Miles Laboratory, Elkhart, IN) stimulation (3.3 +/- 0.7 to 1.3 +/- 0.1; P = .03) and in mixed lymphocyte culture (MLC) (41.5 +/- 8.5 to 16.8 +/- 3.8; P = .02), and during the second week of therapy for in vitro IL-2 stimulation (83.3 +/- 16.8 to 42.9 +/- 12.0; P less than .01). When skin responses were directly compared with in vitro proliferation data, a significant correlation was observed for tetanus (r = .75; P less than .01), streptococcal antigen (r = .83; P less than .01), tuberculin (r = .83; P less than .01), and candida (r = .78; P less than .01). Thus, significant decreases in skin test responses and in vitro proliferation were demonstrated after therapy compared with pretreatment. Flow cytometry revealed marked increases in T-lymphocyte numbers after IL-2 alone (973 +/- 252 to 3,436 +/- 754 cells/mL; P less than .01) and IL-2 receptor-bearing cells (105 +/- 28 to 983 +/- 215; P less than .01), but not in numbers of B-lymphocytes or monocytes. Induced anergy to skin test antigens was seen during a period of relative and absolute T-lymphocyte expansion. We conclude that immunotherapy with high-dose IL-2 with or without activated lymphocytes results in a decreased response to recall antigens during a period in which lymphoid cells with nominal activation markers (Tac, DR) increase.
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PMID:Acute immunologic effects of interleukin-2 therapy in cancer patients: decreased delayed type hypersensitivity response and decreased proliferative response to soluble antigens. 326 51

To investigate the possible involvement of some cell surface structures on lymphoid cells in the functional activity of lymphokine activated killer (LAK) cells, a number of monoclonal antibodies (Mab) against such structures was studied for their ability to inhibit LAK activity in a standard cytotoxicity assay against the natural killer-insensitive target cell EL-4. Almost complete inhibition of LAK activity resulted from incubation with antibodies to the LFA-1 antigen, while blocking of the Lyt 2 antigen reduced cytotoxic activity about 50%. Mab to T-200 gave a weak and inconsistent inhibitory activity, while antibodies to Thy 1, L3T4, IL-2 receptor and MHC class I antigens were without effect. Mab to LFA-1 and Lyt 2 inhibited LAK activity towards EL-4, YAC-1 and differentiated F-9 teratocarcinoma cells, but did not affect LAK-mediated killing of undifferentiated F-9 cells. Experiments with separate preincubation of effector and target cells revealed that both LFA-1 and Lyt 2 inhibited LAK activity at the effector cell level only.
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PMID:Functionally involved cell surface antigens on murine lymphokine activated killer cells. 329 81

The inflammatory cell infiltrate involving synovial tissues from joints affected by rheumatoid arthritis (RA)++ has been contrasted with that present in synovium removed from joints involved by previous trauma (T) or osteoarthritis (OA). Cell deployment has been mapped by immunohistochemistry using monoclonal antibodies which recognise epitopes characterising T and B cells, polymorphonuclear leukocytes, mononuclear phagocytes and platelets. Mononuclear phagocytes were the most consistent feature of the rheumatoid inflammatory cell exudate and were present, particularly in the synovial layer, in all OA/T samples. The synovial cells lacked the C3b complement receptor, CR1, but expressed CR3, the receptor for C3bi. In rheumatoid synovium, interdigitating cells were difficult to identify but cells of dendritic morphology bore at least one macrophage epitope. T cells far out-numbered B cells and generally lacked the IL-2 receptor which is an indicator of T cell activation. Care is required in the estimation of the T helper/inducer (TH) T suppressor/cytotoxic (Ts) ratio. Polymorphonuclear leukocytes were demonstrated around vessels and near the synovial intimal cell layer suggesting rapid tissue transit. Extravascular platelets were sparse. Follicular dendritic cells were defined by their central location in lymphoid follicles and strong expression of CR1 receptors. HLA-DR expression was widespread except on endothelial cells.
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PMID:Lymphocytes, polymorphonuclear leukocytes, macrophages and platelets in synovium involved by rheumatoid arthritis. A study with monoclonal antibodies. 354 69


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