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)

Heat-inactivated (45 degrees C/1 hr) lymphocytes selectively activate suppressor T cells in the mixed lymphocyte reaction (MLR), while no significant proliferation and cytotoxic T lymphocyte activation can be detected. It is not well understood why hyperthermic treatment abolishes the stimulatory capacity of lymphocytes since HLA-DR molecules remain detectable immediately following heat exposure. In order to further characterize the requirements for Ts activation we studied the effects of hyperthermic treatment on cellular protein and DNA synthesis and cell surface protein expression in proliferating T and B cells; interleukin (IL)-1, IL-2, and IL-3 release following allogeneic stimulation with heat treated cells (HMLR); and IL-2 receptor expression as an indicator of T cell activation in the HMLR. Hyperthermic treatment reduced cellular protein synthesis as estimated by 14C-leucine uptake to about 15%, and DNA synthesis (3H-thymidine incorporation) to about 5% of untreated control cells. In contrast to y-irradiated cells, viability of heated cells rapidly declined within the first 24 hr. Hyperthermic treatment doubled binding of mouse immunoglobulin paralleled by an increased expression of IL-2 and transferrin receptors, while expression of HLA-DR and 4F2 proteins appeared unchanged. Stimulation with heated cells triggered the release of IL-1- and an IL-3-like bioactivity but did not induce IL-2 synthesis and/or release, thus explaining the lack of proliferation in the HMLR. Addition of exogenous IL-2 but not IL-1 restored HMLR proliferation. A comparison of allostimulation with y-irradiated and heat-treated cells revealed that significantly fewer T cells were induced to express IL-2 receptors at day 3 (14% vs. 8%, P less than 0.001) and at day 6 (42% vs. 21%, P less than 0.05) with heat-inactivated stimulators. We conclude that metabolically compromised lymphocytes activate Ts and are sufficient to stimulate IL-1 and IL-3 synthesis but do not transmit an unknown signal required for the activation of IL-2 synthesis and IL-2 receptor expression on a yet-to-be-defined T cell subset.
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PMID:Differential effect of gamma-irradiated and heat-treated lymphocytes on T cell activation, and interleukin-2 and interleukin-3 release in the human mixed lymphocyte reaction. 296 Nov 13

We report a new, monocyte-independent system for the induction of activation and proliferation of human T cells in response to murine hybridomas expressing the OKT3 monoclonal antibody (OKT3 hybridomas). Incubation of nylon-wool-nonadherent (NA) lymphocytes or purified T cells with OKT3 hybridomas resulted in interleukin-2 (IL-2) production, expression of IL-2 receptor, modulation of the CD3 antigen, and proliferation. In contrast, murine hybridomas (OKT4, OKT8, anti-HLA-DR, and others) expressing monoclonal antibodies (mAb) other than OKT3 did not induce T-cell activation and proliferation. T cells did not respond to OKT3 mAb alone. OKT3 hybridomas alone did not produce interleukin-1 (IL-1) or other soluble factors that might be involved in the induction of IL-2 production by T cells, and they did not contain membrane-bound IL-1. In addition, IL-1 activity was not detected in cultures of NA-lymphocytes and OKT3 hybridomas, clearly demonstrating that IL-1 was not required, at least in this system, for T-cell activation and proliferation. Direct cell-cell contact between T cells and OKT3 hybridomas was required for IL-2 production. Thirty to fifty percent of T cells formed conjugates with the OKT3 hybridomas but not with the OKT4 or OKT8 hybridomas. Both conjugate formation and IL-2 production were significantly inhibited by the OKT3 mAb and by the anti-LFA-1 mAb. The cells responsible for IL-2 production were found to be of the T3+ T4+ T8- Leu 7- Leu 11- phenotype. IL-2 activity produced by NA-lymphocytes in response to OKT3 hybridomas became detectable as early as 1 hr and reached a maximum by 8 hr, preceding IL-2 receptor expression, modulation of the CD3 antigen, and [3H]thymidine incorporation of T cells. T cells produced higher concentrations of IL-2 in response to OKT3 hybridomas than in response to equal numbers of monocytes and OKT3 mAb. Addition of monocytes to cultures of T cells and OKT3 hybridomas resulted in suppression of IL-2 production in a concentration-dependent manner, suggesting that monocytes regulate the levels of IL-2 production. This monocyte-independent system may be useful for further dissection of T-cell activation and proliferation and its regulation by monocytes.
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PMID:Monocyte-independent interleukin-2 production and proliferation of human T cells in response to murine hybridomas expressing the OKT3 monoclonal antibody: interleukin-1 is not required for T-cell proliferation. 296 76

Nickel sulphate antigen-induced peripheral blood lymphocyte activation in vitro was characterized by lymphokine measurement (IL-2, IFN-gamma) and phenotyping of the IL-2 responsive cells. Mononuclear cells from nickel-sensitive patients synthesized more DNA, produced more IL-2 and had more IL-2 receptor positive cells in response to nickel than did those of the control subjects. On the other hand no IFN-gamma was detectable in the nickel supernatants, while PPD, used as the control antigen, induced pronounced quantities of IFN-gamma with an equal amount of DNA synthesis. The increase in IL-2 receptor positive cells was due to activation of CD4+ (helper/inducer) T cells. T cells with HLA-DR antigen surface markers were more numerous on each day of culture than cells with IL-2 receptors. These two activation markers were co-expressed on the same cells only to a certain extent, thus perhaps reflecting different types or phases of activation. In conclusion, nickel-induced peripheral blood mononuclear cell activation in vitro differs from microbial antigen-induced activation with respect to its modest or non-existent IFN-gamma response.
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PMID:Nickel antigen induces IL-2 secretion and IL-2 receptor expression mainly on CD4+ T cells, but no measurable gamma interferon secretion in peripheral blood mononuclear cell cultures in delayed type hypersensitivity to nickel. 297 21

T lymphocytes were isolated from tumor biopsies in 13 patients with breast carcinomas. Immunohistology with monoclonal antibodies confirmed the presence of mononuclear cell infiltrates composed primarily of T lymphocytes in all tumors studied. While the proportion of T lymphocytes expressing the T4 or the T8 surface marker varied from tumor to tumor as determined by morphometric analysis, T8+ cells were more numerous than T4+ cells in 8/12 breast tumors studied. Relatively few T cells (less than 10% in 11/12 tumors) were in an activated state as judged by the surface expression of HLA-DR antigens or the receptor for interleukin-2 (IL-2). In 1 case 20% of the infiltrating mononuclear cells were expressing the IL-2 receptor. The tumor infiltrating lymphocytes (TIL) recovered from 10 tumors were cloned in a microculture system that permits proliferation of nearly 100% of normal peripheral blood T lymphocytes (PBL-T). In contrast to normal and autologous PBL-T, frequencies of proliferating T lymphocyte precursors (PTL-P) were depressed (less than 0.01) in 7/10 TIL preparations indicating a decreased responsiveness of TIL to phytohemagglutinin at the single-cell level. The frequency of PTL-P was noticeably higher in 2 cases (0.03 and 0.09) and close to normal in 1 case (0.39). A total of 170 clones were expanded in vitro and analyzed for different functional capabilities. Most of these clones expressed the T4+/T8-phenotype (73%) and strikingly 53% of these T4+/T8- clones were cytolytic in a lectin-dependent assay, a functional subset which is uncommon among normal PBL-T. Some clones (10%) lysed allogeneic breast tumor cells (MCF7). Only 15% of the clones displayed natural killer activity. Among the cytolytic clones, 17 of 31 tested were also IL-2 producers irrespective of the T4 or T8 phenotype. Our results show that human mammary carcinomas contain many infiltrating T cells with cytolytic potential. Interestingly, among the proliferating cytolytic T cell clones (56% of the microcultures), many expressed the T4+/T8- phenotype. These findings may indicate that the in situ cytolytic reaction (against unknown antigens) is associated preferentially with class II antigens.
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PMID:Clonal analysis and in situ characterization of lymphocytes infiltrating human breast carcinomas. 302 32

Giant cell arteritis (GCA) is a vascular inflammatory disease characterized by accumulations of T lymphocytes and macrophages in the arterial wall. In order to characterize the immune response in GCA, we have analysed temporal artery biopsies using a double-staining immunofluorescence method and studied T lymphocytes in peripheral blood with a fluorescence-activated cell sorter (FACS). HLA-DR was expressed on 28% (range 16-42%) of all T lymphocytes in the wall of the inflamed temporal artery, but only on average on 6% of peripheral blood T lymphocytes, indicating a high degree of local T cell activation in the inflammatory lesion. The proportions of T lymphocytes, T helper/inducer and T suppressor/cytotoxic cells in the blood of GCA patients before treatment with prednisolone did not deviate from those in normal individuals, but there was a minor increase in T helper cells after initiation of steroid therapy. The number of T helper cells expressing HLA-DR antigen and IL-2 receptor was not altered after 6-10 days of treatment with prednisolone. We found no evidence of HLA-DR expression by arterial smooth muscle cells in the GCA lesions, suggesting that these cells do not serve as antigen-presenting cells in GCA.
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PMID:HLA-DR expression in the vascular lesion and circulating T lymphocytes of patients with giant cell arteritis. 304 14

The present investigation was conducted in order to examine the feasibility of isolating and growing glioma-infiltrating lymphocytes in vitro as possible effector cells for use in new adoptive immunotherapy. Eight surgical specimens obtained from patients with malignant astrocytomas were treated by enzyme dispersion; the cells were separated on a density gradient and grown in the presence of human recombinant interleukin-2. The cultured lymphocytes were tested for cell-surface markers by using monoclonal antibodies in a flow cytometric analysis. In all cases the glioma-derived lymphocytes were grown in culture for several weeks with substantial increases in cell numbers (at least 5 X 10(8) cells). The mature T cell population (CD3, 89%) was found to have an increased proportion of the cytotoxic/suppressor phenotype CD8 (55%) as compared to peripheral blood lymphocytes (PBL's). Eighty-six percent of the cultivated lymphocytes expressed HLA-DR. The IL-2 receptor was predominantly expressed on the helper subset (CD4-positive). Otherwise, anti-CD16, which specifically reacts with natural killer (NK) cells, did not stain significantly more of the cultured gliomaderived lymphocytes compared with lymphocyte-activated PBL's. These results corroborate the observations made with conventional immunohistochemical examination. It has been demonstrated that T lymphocytes isolated from human cancers are enriched for specific reactivity to their autochthonous tumor cells. These experiments support the possible use of glioma-infiltrating lymphocytes as a new treatment for patients with malignant glioma.
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PMID:Isolation and in vitro growth of glioma-infiltrating lymphocytes, and an analysis of their surface phenotypes. 305 14

The expression of activation antigens (transferrin receptor, IL-2 receptor and Ia antigen) on circulating T lymphocytes from Japanese children with Type 1 diabetes was studied using five monoclonal antibodies (Ab), OKT9, anti-Tac Ab, OKIa1, anti-human HLA-DR Ab and OKT3. For detecting Ia positive T cells, the dual staining technique using OKT3 and anti-Ia antibody was employed. Four out of six patients (67%) with newly diagnosed Type 1 diabetes showed a raised level of either OKT9 or Tac positive cells when examined at diagnosis. These patients, however, rapidly lost these activation antigens after the insulin therapy was started. In contrast, in 32 long-standing patients, only 2 (6%) had a high percentage of OKT9 positive cells and none of them demonstrated Tac positive cells. One out of six newly diagnosed patients or three out of 21 long-standing patients had a significantly high percentage of Ia-positive T cells compared with normal subjects. In poorly controlled long-standing patients whose HbA1 value was higher than 14%, none of them had an increased number of activated lymphocytes. Therefore, it is unlikely that insulin deficiency and hyperglycemia were responsible for the changes observed in these studies. Activated lymphocytes might be related to activation of the immune system involved in pathogenesis of Type 1 diabetes.
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PMID:Activated lymphocytes in patients with newly diagnosed type 1 (insulin-dependent) diabetes mellitus. 309 6

The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen-induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures decreased significantly after 48 h of stimulation with mitogen compared with that of 24 control cultures. The lymphocyte responses to phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) increased linearly with time, but the responses of the uraemic cell cultures were significantly lower than those of the control cultures. The relative numbers of cells double-stained for both Tac (IL-2 receptor)/HLA-DR or Tac/Leu 2 were significantly increased in the uraemic cultures as compared with the control cultures at 48 and 72 h. A similar, but not significant, trend was also demonstrated for uraemic cells positive for Tac/Leu 3. These findings were also seen in uraemic lymphocyte cultures supplemented with exogenous IL-2. Thus, the IL-2 production of uraemic lymphocytes seems to be exhausted more rapidly than that of normal lymphocytes, and there is no evidence that the poor proliferative response of uraemic lymphocytes is due to a decreased relative number of cells positive for IL-2 receptors.
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PMID:Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes. 310 Nov 70

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

Twenty-two patients with adult onset aplastic anaemia were analysed before and after therapy with anti-thymocyte globulin (ATG). Lymphocyte phenotype, lymphokine levels or production, and haematopoietic progenitor cell number were measured 3 months after therapy; clinical response was determined 1 year post-therapy. By flow cytometry there was a significant reduction in both the proportion and absolute number of peripheral blood lymphocytes expressing activation antigen Tac (IL-2 receptor) and in the proportion of HLA-DR+ lymphocytes. For T cells bearing HLA-DR, there were proportional decreases in both activated helper and suppressor cells. There was no statistically significant difference pre-ATG to post-ATG in the absolute numbers of total, helper and suppressor lymphocytes. In all 10 haematologic responders the number of Tac bearing lymphocytes after ATG therapy was in the normal range, but half of 12 non-responding patients continued to have abnormally elevated numbers of Tac+ T cells. The proportion of Tac+ cells were not related to transfusion history. Gamma-interferon levels in serum by radioimmunoassay were elevated in almost half the aplastic patients; post-ATG, gamma-interferon was detectable in only three patients. Haematologic response to ATG therapy was associated with increased numbers of haematopoietic progenitors post-treatment, but pre-treatment values were not predictive of a response. These results are consistent with a pathogenic role for activated T-cells and their lymphokine products and suggest that the target of ATG therapy may be a Tac+ lymphocyte.
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PMID:Lymphocyte phenotype and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anaemia. 311 88


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