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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A 57-year-old man with a history of recurrent infections from the age of 50 was hospitalized with a diagnosis of common variable hypogammaglobulinemia (CVH). Immunological studies revealed a severe reduction of circulating immunoglobulins of all classes. Immunophenotyping of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies, revealed normal values of total B and T cells with CD4/CD8 ratio sharply reduced (0.35) as compared to normal (1.6) because of an increase of CD8 and a decrease of CD4 cells. The surface expression of IL-2 receptor was normal. Natural cytotoxic and phagocytic system presented several abnormalities: a deep impairment of NK activity was found in spite of a normal number of NK cells, as ascertained by Leu 19 and B73.1 monoclonal antibodies. The defective NK activity was not restored by interferon alfa, but was normalized by recombinant IL-2. Phagocytic function, as defined by zymosan-stimulated O2- production was almost absent. The involvement of natural cytotoxic and phagocytic systems in CVH has been rarely reported; the possible causative role of a chronic viral infection (Epstein-Barr virus?) is discussed, on the base of anamnesis.
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PMID:NK cell activity and monocyte dysfunctions in a patient with common variable hypogammaglobulinemia. 297 23

Our method of adoptive immunotherapy (AIT) using autologous IL-2-cultured lymphocytes differs from so-called LAK therapy in several points. We (1) obtain cultured lymphocytes from effusion lymphocytes (EL) or regional lymph-node lymphocytes (RLNL), when possible, rather than peripheral blood lymphocytes (PBL), (2) use crude IL-2 to induce T cell proliferation and to maintain killer activity, (3) use sonicated autologous tumor extract as antigen (Ag) to stimulate proliferation of cytotoxic T cells, and (4) pretreat the patients with local administration of OK-432 before AIT to induce effector cells that act synergistically with transferred killer cells. Surface marker analysis showed that OKT3, IL-2 receptor, Leu 2+15- cells were elevated while Leu 11a and Leu 3+8+ cells were decreased. Culture of RLNL augmented the expression of Leu 3+8- marker. Both of PBL and RLNL responded to Ag, and their auto-tumor killing activities were augmented in about half of the patients while rarely decrease by the addition of Ag. Response rates of patients with pleural effusion due to breast cancer and those with liver metastasis of breast cancer were 94% and 60%, respectively. Moreover, the survival was prolonged in the treated patients with pleural effusion or gastric cancer patients with peritoneal dissemination.
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PMID:[Clinical therapeutic effect of adoptive immunotherapy using IL-2-cultured autologous lymphocytes]. 297 6

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

Receptors for interleukin 2 (IL-2) are absent on resting T lymphocytes and are induced by antigenic and mitogenic stimulation. After a limited time (8-12 days), these receptors on normal T cells are down-regulated despite the presence of receptor-saturating concentrations of IL-2. We report here that both antigen- and mitogen-induced T-cell lines and clones obtained from peripheral blood and cerebrospinal fluid of multiple sclerosis patients show prolonged expression of IL-2 receptors. This expression is coincident with a prolonged responsiveness to the proliferative effects of IL-2. In addition, Leu 3+, IL-2 receptor-positive T-cell clone from the cerebrospinal fluid of a multiple sclerosis patient has been established and maintained for more than 1 year without IL-2. This clone has some morphologic and histochemical properties of T cells transformed or infected by human T-lymphotropic virus type I.
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PMID:Regulation of interleukin 2 receptors on T cells from multiple sclerosis patients. 308 2

Peripheral blood mononuclear cells from 25 patients with measles and 13 patients with other diseases from Lima, Peru, were studied by immunocytochemical staining for cell surface antigens indicating the type of cell (Leu 4, Leu 3, T8, B1, M1, or esterase) and the state of cell activation (T10 and IL-2 receptor). Measles patients were studied during the first 2 weeks of disease and had no alteration in the proportion of cells which were positive for any subset marker or in the ratio of helper/inducer to cytotoxic/suppressor T cells compared to controls. Measles patients, however, had a greater number of cells expressing the activation antigens T10 and IL-2 receptor than controls. Incorporation of [3H]thymidine was also higher in measles patients when exogenous natural or recombinant IL-2 was added to unstimulated cultured cells. We conclude that the peripheral blood mononuclear leukocytes of patients with measles have normal proportions of helper/inducer and cytotoxic/suppressor T lymphocytes, B lymphocytes, and monocytes but that an increased number of these cells are in an activated state.
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PMID:Peripheral blood mononuclear cells during natural measles virus infection: cell surface phenotypes and evidence for activation. 308 68

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

The present study was undertaken in an attempt to reconcile the conflicting results concerning the signals required for the activation of human resting T cells by antibodies to the T-cell receptor/CD3 complex (Ti/CD3). For this purpose we have used highly purified peripheral blood T cells, depleted of monocytes and of preactivated Ia + T cells, to the extent that they were unable to proliferate to interleukin 2 (IL-2) alone or to optimal doses of phytohemagglutinin (PHA). To further minimize the contribution of contaminating monocytes, we used the anti-CD3 mAb, Leu-4, and cells from Leu-4 nonresponder subjects, whose monocytes we show completely fail to bind the Leu-4 mAb. The parameters of T-cell activation which we measured were rises in intracellular free calcium ion [Ca2+]i, IL-2 receptor expression IL-2 production, and cell proliferation. Our results indicate that induction of proliferation of resting T cells requires at least two signals. Signal one is best delivered by multivalent anti-CD3 mAb, such as Leu-4 mAb covalently linked to Sepharose 4B (Seph-Leu-4), or with Leu-4 mAb and anti-mouse IgG. These reagents crosslink the CD3 receptor complex on the T cell, and result in a rise in intracellular [Ca2+]i, in expression of receptors for IL-2, and in proliferation upon addition of IL-2. In contrast, purified T cells exposed to soluble Leu-4 mAb do not exhibit a rise in intracellular [Ca2+]i, do not express receptors for IL-2, and do not proliferate upon addition of IL-2, indicating that the valency of anti-CD3 mAb is critical for the delivery of the first activation signal to the T cell. The essential step of crosslinking of CD3 antigens on T cells by anti-CD3 mAb is normally mediated by monocytes which have bound anti-CD3 mAbs via their Fc receptors. Monocytes from Leu-4 nonresponder subjects, which we show fail to bind Leu-4 mAb, fail to crosslink CD3 antigens on T cells, resulting in failure of T-cell activation. The second signal needed for the proliferation of T cells whose Ti/CD3 complexes are crosslinked is IL-2. IL-2 production by such T cells required a monocyte delivered signal, which must be delivered to these T cells simultaneously with the crosslinking of their Ti/CD3 antigens. This IL-2-inductive signal can be delivered by both Leu-4 nonresponder and Leu-4 responder monocytes, indicating that delivery of this IL-2 inductive signal is independent of anti-CD3 mAb binding by monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Requirements for activation of human peripheral blood T cells by mouse monoclonal antibodies to CD3. 310 59

In this study, we sought to elucidate the sequence of events by which mitogenic monoclonal anti-CD3 antibodies (anti-CD3-MoAb) initiate T cell activation. In cultures of monocyte-depleted resting T cells, two anti-CD3-MoAb, OKT3 and anti-Leu 4, induced a state of interleukin 2 (IL-2) receptiveness which culminated in T lymphocyte proliferation when recombinant IL-2 was provided. Evidence that Fc-receptor mediation by monocytes did not contribute to this mitogenesis was supported by studies showing that polyclonal F(ab')2 anti-mouse IgG Fc antibody did not alter the magnitude of the IL-2 driven T cell proliferative response, and by the use of T cells from donors whose monocytes were unable to assist in the induction of anti-Leu 4 (IgG1 subclass) initiated proliferation. Anti-CD3-MoAb, in the absence of IL-2, induced IL-2 receptor expression on purified T cells, and anti-IL 2 receptor antibodies inhibited T cell proliferation in the presence of this growth factor. Furthermore, following modulation of the CD3 molecular complex in the presence of monocytes, depletion of accessory cells rendered the modulated T cells mitogenically dependent on exogenous IL-2. IL-2 itself did not suffice to promote T cell proliferation in the absence of anti-CD3-MoAb. These results indicate that the binding of monoclonal antibody to CD3 is capable of initiating, in an accessory cell-independent manner, premitotic alterations in T cells which can culminate in proliferation when exogenous IL-2 is provided.
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PMID:Induction of interleukin 2 receptiveness and proliferation in resting peripheral T cells by monoclonal anti-CD3 (T3) antibodies does not require the presence of macrophages. 311 39

Recombinant human interleukin-2 (rIL-2) was administered to 34 patients with advanced malignancy. Three schedules of rIL-2 administration employed were as follows: (A) 2-hr iv infusion of 6.7 X 10(5) U/m2/day (A1, 6 cases) or 2.2 X 10(6) U/m2/day (A2, 8 cases) for five consecutive days; (B) 24-hr continuous iv infusion of 3.3 X 10(5) U/m2/day (B1, 3 cases), 6.7 X 10(5) U/m2/day (B2, 7 cases) or 1.1 X 10(6) U/m2/day (B3, 5 cases) for 28 consecutive days; and (C) 24-hr continuous iv infusion of 6.7 X 10(5) U/m2/day (C, 5 cases) for 5 consecutive days per week for four weeks. The common side effects were fever (79%), eosinophilia (61%), malaise (56%), erythema or rash (50%), chills (38%) and nausea or vomiting (35%), with the dose-limiting toxicities being hypotension in group A, and renal dysfunction with fluid retention in groups B and C. In the case of 2-hr iv infusion, rIL-2 was rapidly cleared from the plasma, with a half life of about 30 min, while in the case of 24-hr continuous infusion, more than 1 U/ml serum IL-2 activity was maintained for 14 days in group B3. Natural killer (NK) and lymphokine-activated killer (LAK) activities were augmented by rIL-2 administration in patients of groups A, B3 and C. In eight patients of group B, NK and LAK activities transiently decreased after rIL-2 administration, and recovered by day 3. The percentage of IL-2 receptor and Leu HLA-DR positive cells reached the peak level on day 7 in group B. In patients of group C, the percentage of Leu HLA-DR positive cells as well as NK and LAK activities increased upon rIL-2 administration and decreased during an intermission of two days. However, the percentage of rIL-2 receptor positive cells increased during the intermission of rIL-2. The most effective schedule of rIL-2 administration was considered to be the schedule of group C on the basis of this study.
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PMID:Three schedules of recombinant human interleukin-2 in the treatment of malignancy: side effects and immunologic effects in relation to serum level. 312 1


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