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

Studies were undertaken to evaluate the effect of hepatitis B virus (HBV) immune complexes (HBV-IC) on IL-2 dependent human lymphocyte proliferation. The following parameters were studied: 1) Effect of HBV-IC (HBsAg-IgG or HBeAg-IgG) on PHA-mediated lymphocyte proliferation; 2) Influence of HBV-IC on the ability of PHA-stimulated peripheral blood lymphocytes (PBL) for IL-2 production and IL-2 receptor expression. HBV-IC induced a dose dependent and antigenic dependent suppression of PHA stimulated lymphocytes. The suppressor effect exerted by HBsAg-IgG was irreversible. In contrast, the suppression mediated by HBeAg-IgG was reversible: lymphocytes preincubated with this preparation washed and activated with PHA responded well to mitogen. The presence of HBV-IC in the cultures of PHA-activated PBL decreased their ability to produce IL-2: HBeAg-IgG exerted a stronger suppressor effect. This effect was partially reversible: removal of HBV-IC from the culture by washing and subsequent stimulation of PBL with PHA increased the capacity of lymphocytes to produce IL-2. This was particularly evident with HBeAg-IgG. Decreased activity of IL-2 observed in the cultures, was also partially dependent on the ability of HBV-IC to bind IL-2 present in the culture medium. Experiments performed using ultracentrifugation indicated that HBV-IC, especially HBsAg-IgG, may bind to IL-2 and inactivate it. HBV-IC had also an effect on IL-2 receptor expression: 1) their presence in the cultures of PHA-stimulated PBL decreased the number of Tac positive cells; 2) the response of HTCL to exogenous IL-2 was decreased by HBV-IC present in the culture medium. This was especially observed in the case of HBsAg-IgG. We suggest that the observed inhibition of PHA-induced lymphocyte proliferation exerted by immune complexes containing HBsAg-IgG or HBeAg-IgG may be caused mainly by their influence on IL-2 dependent mechanism of lymphoproliferation.
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PMID:Influence of immune complexes containing HBsAg and HBeAg on IL-2 dependent human lymphocyte proliferation. 234 99

In this paper, we have described the effects of tumor-derived immunosuppressive factor(s) (TDSF) on interleukin 2 (IL-2) production, on IL-2 responsiveness and on the expression of IL-2 receptors. The results showed that TDSF was able to markedly inhibit the production of IL-2 from PHA-stimulated lymphocytes and IL-2-dependent proliferation of activated lymphocytes, and to partially inhibit the expression of IL-2 receptor. These results suggest that inhibiting IL-2 production and responsiveness may be a major mechanism by which TDSF inhibit T lymphocyte proliferation and other immune responses. That TDSF exerted a very potent inhibiting action on IL-2 responsiveness is especially noticeable if we consider using IL-2 as an immunotherapeutic agent. This may be an important reason why treatment of tumor with IL-2 did not yield satisfactory results so far.
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PMID:Effect of tumor-derived immunosuppressive factor(s) on interleukin 2 and on expression of interleukin 2 receptor. 234 88

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.
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PMID:A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. 240 92

The role of distinct regions of HLA class I molecules in regulating T-cell activation via the CD3-antigen receptor complex was investigated. Monoclonal antibodies (MoAbs) which recognize monomorphic and polymorphic epitopes on HLA Class I molecules were shown to inhibit T-cell proliferation to OKT3. These MoAbs have differential effects on the synthesis of interleukin-2 (IL-2) and IL-2 receptor expression. Cell cycle analysis demonstrated that these MoAbs function both in inhibiting cell cycle entry (G0-G1 shift) and in blocking cell cycle progression (G1-S shift) of activated T cells. Furthermore, these MoAbs have regulatory effects on the alternate pathway of T-cell activation via the CD2 molecule, T-cell activation induced by PHA, and activation induced by the phorbol ester PMA in conjunction with the calcium ionophore Ionomycin. Thus these MoAbs have different effects depending upon the pathway of T-cell activation. The results indicate that HLA class I molecules are selectively involved in the sequence of intracellular events leading to T-cell activation and proliferation.
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PMID:CD3 pathway of T-cell activation. II. Role of HLA-class I molecules in early events. 245 48

The effect of FK506 on in vitro human lymphocyte responses was assessed in comparison with cyclosporine. FK506 suppressed, in a dose-dependent fashion, the lymphocyte response to stimulation with PHA and with alloantigens in primary mixed lymphocyte reactions at a 70-100-fold lower concentration than CsA--namely, 50% inhibition (IC50) was obtained with 8.6 nM FK506 and with 750 nM CsA in the PHA response, and with 0.21 nM FK506 and with 20 nM CsA in MLR. Allocytolytic T lymphocyte induction was also inhibited by FK506, whereas the ability of CTL to lyse targets was not affected by the agent, indicating that FK506 did not affect the recognition and binding of alloantigen by CTL. FK506 inhibited, in a dose-dependent fashion, both IL-2 receptor and transferrin receptor expression on the alloactivated lymphocytes--whereas this agent inhibited only incompletely both expression of both receptors on lymphocytes stimulated with PHA. Lymphocytes from primary MLR cultured in the presence of FK506 were tested for suppressor cell activity on day 8 of culture. FK506 did not allow for the expression of alloantigen-activated suppressor cells when used in a dose sufficient to inhibit CTL generation.
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PMID:Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. I. Inhibition of expression of alloantigen-activated suppressor cells, as well as induction of alloreactivity. 246 92

To evaluate cell mediated immunopathogenic mechanisms in chronic hepatitis B virus (HBV) infection, we investigated the changes of T4/T8 ratios from the peripheral blood, the percentages of IL-2 receptor expression after stimulation of mitogens (Con A, PHA) and a specific antigen (Hepatitis type B surface antigen, HBs), and the proliferative response mediated by IL-2 receptors after rIL-2 stimulation on mixed mononuclear cell. These experiments were performed comparatively in 5 groups which consisted of serologically negative normal subjects, chronic HBV carriers, patients with chronic active hepatitis (CAH) type B, patients with acute hepatitis (AH) type B, and the antibody positive healthy subjects. There were significant decreases of T4/T8 ratios in chronic HBV carriers, in patients with CAH type B, and in patients with AH type B, compared with negative normal controls. There were no significant differences between patients with CAH type B and the HBs negative normal controls in the percentage of IL-2 receptor positive cells after in-vitro HBs-stimulation and the proliferative response assessed by the incorporation of 3H-thymidine, whereas in patients with AH type B there were significant increases in both. Thus, in addition to a relatively decreased T4/T8 ratio, the impairment of IL-2 receptor expression on the lymphocytes after HBs-stimulation caused a defective response of cellular proliferation, and this might be one of the leading immunopathogenic roles in chronic HBV infection.
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PMID:Impaired interleukin-2 receptor expression on lymphocytes from patients with chronic active hepatitis type B. 248 3

In this study, we describe a new methodology to detect and quantify lymphokine receptors, using interleukin-2 as a prototype. Human recombinant interleukin-2 (IL-2) was conjugated to fluorescein isothiocyanate. Binding of fluoresceinated IL-2 to different cell types was assessed by flow cytometry analysis, on a FACS 440 calibrated using fluoresceinated Sephadex G-25 beads. This calibration procedure allowed us to quantify the actual number of binding sites for IL-2. Fluoresceinated IL-2 did not bind to normal resting T cells, whereas a highly significant binding was observed on PHA-activated human T cells. The binding was inhibited by an excess of unlabeled IL-2 and by an excess of anti-IL-2 receptor p55 antibodies (anti-TAC). Dose curves of IL-2 showed a two plateau saturation, the first plateau corresponding to the saturation of high affinity binding sites, as assessed by correlation with the biological activity on IL-2-dependent T cells. Among the cell types tested, fluoresceinated IL-2 bound to IL-2-dependent mouse T cells (the binding in that case was not inhibited by anti-IL-2 receptor p55 antibodies), and to different p70 expressing cell lines or normal cells (MLA 144, normal large granular lymphocytes). Taken together, these results indicate that fluoresceinated IL-2 can be used to detect high as well as low affinity IL-2 binding sites.
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PMID:Detection of low and high affinity binding sites with fluoresceinated human recombinant interleukin-2. 249 69

It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) reactions by depleting tissue mast cells of serotonin, thereby preventing a T cell-dependent release of mast cell serotonin necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. Recently, we showed that the ability of reserpine to interfere with the expression of contact sensitivity was independent of an effect on mast cells, but reflected an effort of the drug on effector T cell function. In the present study we evaluated the mechanisms by which reserpine abrogates the expression of T cell functions. By using human peripheral blood mononuclear cells or enriched T cell populations we found that the drug inhibited, in a dose-dependent fashion, the proliferation of T cells after mitogen stimulation. Reserpine also interfered with the mitogen-induced IL-2 production by these cells, but the IL-2 receptor expression, as measured by immunofluorescence, was unaffected. Despite this, in the continuous presence of reserpine, exogenous IL-2 did not bypass reserpine inhibition of PHA-induced proliferation. By using the fluorescent indicator quin-2 we have demonstrated that preincubation with reserpine prevented the increase of cytosolic free calcium, which accompanies PHA-induced proliferative responses of human T lymphocytes. These results identify the sites of action of reserpine in human T lymphocytes and are sufficient to explain its ability to block cell-mediated immune responses in vitro and in vivo.
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PMID:Characterization of the interference of T cell activation by reserpine. 251 Sep 39

To assess the role of decidual cells (DC) in the maintenance of pregnancy, immunosuppressive activity of culture supernatants from human DC were investigated. Dispersed DC suspensions from decidual tissue of early pregnancies were prepared by an enzyme digestion method using collagenase and DNase, and were enriched over 90 per cent without contamination of macrophages and lymphocytes in the fraction, with specific gravity between 1.033 and 1.044 (fraction 2 [Fr2] ) by a Percoll discontinuous density gradient method. The culture supernatants of Fr2 cells suppressed the responses of normal peripheral blood lymphocytes to PHA, MLR, and killer T cell generation at the 50 per cent concentration. To determine the mechanism of the immunosuppressive activity of the culture supernatants, the effect of the supernatants on interleukin-2 and gamma-interferon production, as well as IL-2 receptor expression, on PBL was investigated. The supernatants from 3 x 10(6)/ml of DC cells inhibited not only IL-2 and gamma-INF production, but also IL-2 receptor expression, compared with normal controls. The supernatants also suppressed immunoglobulin (IgG and IgM) production by pokeweed mitogen-stimulated B cells. To purify the suppressor factor from culture supernatants of DC, serum free culture supernatants of 3 x 10(6)/ml of DC, which showed 32 per cent of inhibitory activity on MLR, were applied to gel filtration. Fractions between mw 67,000 and 43,000 suppressed the MLR. These results suggest that DC from decidua of early pregnancy excrete an immunosuppressive factor with a molecular weight between 43,000 and 67,000 daltons.
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PMID:Characterization and analysis of soluble suppressor factor from early human decidual cells. 252 5

HIV infection is known to induce a progressive T helper/inducer (CD4) lymphopenia and to impair the functional activities of residual cells. The present studies examined the relationship between the CD4 cell count and three functional assays: T cell colony formation in semisolid media, the capacity of PHA-stimulated cells to express IL-2 receptors, and their ability to synthesize and secrete IL-2. Cells from antibody-positive homosexuals with normal numbers of CD4 cells (greater than 700/microliters) showed defective reactivity in two assays, colony growth, and IL-2 receptor expression. These defects became progressively more pronounced in homosexuals with moderate (400-700 cells/microliters) and severe (less than 400/microliters) reductions in assays for IL-2 production by PHA-stimulated lymphocytes. Mixing experiments suggest that cells from HIV-infected men nonspecifically inhibit the colony growth of normal cells; this abnormality could be reversed by addition of exogenous IL-2. These data suggest that defective colony growth and reduced IL-2 expression are functional abnormalities directly resulting from HIV infection. Furthermore, these changes can precede the CD4 lymphopenia induced by this viral infection.
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PMID:Defective T cell colony formation and IL-2 receptor expression in HIV-infected homosexuals: relationship between functional abnormalities and CD4 cell numbers. 252 69


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