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 U937 suppressor factor (U937SF) was purified from crude supernatant by sequential chromatography using fast protein liquid chromatography. The molecular weight and isoelectric point of U937SF were 69 kDa and 4.5, respectively. The U937SF preparation inhibited the proliferative response in human PBMC stimulated with an antigen tuberculin purified protein derivative, tetanus toxoid) or a mitogen (phytohaemagglutinin concanavalin-A). U937SF depressed both interleukin-2 (IL-2) production and IL-2 receptor (CD25) expression in peripheral blood mononuclear cells (PBMC) stimulated with an antigen but not with a mitogen. Anti-CD3 monoclonal antibody-induced responses including a proliferative response, IL-2 production and CD25 expression were suppressed by U937SF. In contrast, U937SF did not affect monocyte functions such as antigen processing and IL-1 production. Neither did it modulate the expression of T cell receptor (TCR) or CD3 molecules on the surface of lymphocytes. Moreover it did not inhibit CD25 expression in PBMC stimulated with phorbol myristate acetate plus A23187. These results suggest that U937SF prevents both IL-2 production and CD25 expression in lymphocytes activated through the TCR/CD3, but not through the other receptors or molecules. In addition, U937SF does not block the early activation events following TCR-mediated stimulation, nor affect the pre-TCR activation steps.
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PMID:Pattern of the action of a suppressor factor produced by a human macrophage-like cell line, U937. 139 77

Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID.
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PMID:Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency. 163 64

A whole inactivated H. pylori bacterium preparation was found to stimulate blood mononuclear cells from both antibody-positive and antibody-negative subjects, but the antibody-positive subjects tended to have lower proliferation responses. The present study was designed to characterize T cell activation further by measuring several components of the response. Eighty-seven subjects (80 dyspeptic patients and seven healthy persons from the laboratory staff) with or without antibodies to H. pylori were studied by measuring the DNA synthesis induced by several H. pylori concentrations (1-23 micrograms/ml) and the control stimulants PPD, tetanus toxoid and pokeweed mitogen (PWM). H. pylori-induced secretion of interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), soluble CD8 and IL-2 receptor (IL-2R) molecules and H. pylori- and PPD-induced appearances of IL-2R+ and HLA-DR+ T cells were measured in a smaller number of subjects. H. pylori-induced DNA synthesis was again lower in the antibody/bacterium-positive subjects, while no differences between the two groups were found in cultures stimulated by unrelated antigens or PWM. Soluble IL-2R and TNF-alpha were detectable in cultures with H. pylori from all subjects, while the amount of IL-2 did not differ from that in the background culture. No differences were found in the amounts of IL-2 or soluble IL-2R between the antibody-positive and negative subjects; while the former tended to secrete more soluble CD8 molecules, a difference which was significant with the smaller H. pylori concentration used (P less than 0.01). The numbers of HLA-DR+ and IL-2R+ T cells increased in cultures with H. pylori or PPD from all the subjects, the majority of both cells having the CD4 phenotype. Numbers of DR+ and IL-2R+ T cells were similar in the cultures of the antibody-positive and negative subjects, but the respective CD8 subsets were increased in the former. The confirmed decrease in proliferation in the antibody-positive subjects does not seem to be connected with lower IL-2/IL-2R responses but may involve CD8 cell activation.
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PMID:Blood lymphocyte proliferation, cytokine secretion and appearance of T cells with activation surface markers in cultures with Helicobacter pylori. Comparison of the responses of subjects with and without antibodies to H. pylori. 190 Jul 43

Recombinant diphtheria toxin-related interleukin-2 fusion protein (DAB486IL-2) is specifically cytotoxic for cells bearing the high-affinity IL-2 receptor (p55/75). We evaluated the effects of DAB486IL-2 on the generation of tetanus toxoid (TT)-specific IgG antibody-forming cells in 6-day cocultures of human splenocytes and TT-coupled Sepharose beads. The results indicate that a significant portion (30-75%) of the anti-tetanus toxoid IgG response in vitro was susceptible to inhibition by 10(-10) M DAB486IL-2. The inhibition required both the IL-2 portion of the fusion protein and an active toxin moiety and was greater when the IL-2 toxin was added on Day 3 as compared with Day 0 of culture. The induction of the p55 (Tac) subunit of the IL-2R was demonstrable by two-color flow cytometry on a small percentage (5%) of B cells and on a higher percentage (10%) of non-B cells 3 days after exposure to TT-coupled Sepharose. Short-term (2 hr) treatment of T and B cell subpopulations separated on Day 3 of culture followed by remixing indicated that while activated T helper cells were most strongly inhibited by DAB486IL-2, up to 50% of the TT-specific IgG response was inhibited by treatment of B cells alone with DAB486IL-2. Our results suggest that a strategy of eliminating human memory B cells by a combination of antigen activation and properly timed administration of a recombinant lymphokine-toxin fusion protein is feasible.
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PMID:Inhibition of human antigen-specific memory B cell response in vitro by a diphtheria toxin-related interleukin 2 fusion protein. 198 63

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.
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PMID:Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA. 231 27

Interferon (IFN)-alpha and IFN-beta ("type I" IFNs), but not IFN-gamma reduced phytohemagglutinin- or pokeweed mitogen (PWM)-induced proliferation in cultures of human mononuclear leukocytes. Proliferation induced by specific antigens (tuberculin PPD or tetanus toxoid) or by exogenous interleukin 2 (IL-2) was strongly inhibited by type I IFNs and, to a lesser extent, by IFN-gamma as well. Inhibition of proliferation in mitogen-stimulated cultures was not due to a reduced production of IL-2 or to an inhibition of IL-2 receptor expression. Type I IFNs inhibited immunoglobulin (Ig) production in PWM-stimulated unseparated mononuclear cells, whereas IFN-gamma enhanced Ig production in such cultures. In cultures of purified B cells type I IFNs caused a stimulation of Ig production and this B-cell differentiation factor (BCDF)-like activity of IFNs was synergistically enhanced in the presence of IL-2. IFN-gamma produced less BCDF-like activity than type I IFNs. These results show that in some instances type I IFNs can be more potent in affecting functions of cells of the immune system than IFN-gamma.
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PMID:Modulation of lymphocyte proliferation and immunoglobulin synthesis by interferon-gamma and "type I" interferons. 309 92

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

Experiments were designed to examine the effects of pregnancy-associated growth factor (PAGF), a substance found in commercial preparations of crude human chorionic gonadotropin (hCG), on unfractionated human cord blood cells (CBC) and adult peripheral blood lymphocytes (PBL) cultured in 5% fetal calf serum (FCS). Comparisons of PAGF-induced [3H]TdR incorporation in nine pairs of simultaneously cultured CBC and PBL with phytohemagglutinin (PHA) and tetanus toxoid (TT) showed that all CBC and PBL responded to PAGF and PHA whereas all PBL and one CBC responded to TT. The rank order of potency for CBC and PBL was PHA greater than PAGF greater than TT. To examine phenotypic changes induced by PAGF, flow cytometry was performed on precultured cells, control cultures, and PAGF-stimulated cultures at 2, 5, 7, and 9 days. The monoclonal antibodies (mAbs) included T3, T4, and T8 (T cells), T9 (transferrin receptor), Tac (IL-2 receptor), 12 (Ia or DR-framework antigen), and T10 (putative activation and/or maturation antigen). PAGF-stimulated cultures had statistically significant increased percentages of T3, T4, T9, T10, and Tac but not T8 when compared to precultured cells and control cultures. PAGF also increased PBL but not CBC Ia. In PAGF-stimulated cultures, CBC had more T3 and T4 cells with increased fluorescence intensity than PBL. Maximal expression of phenotypes usually occurred at Days 7 and 9, 2 days after maximal [3H]TdR incorporation. In comparison to PAGF, PHA-stimulated PBL had earlier expression of these phenotypes but included T8. These data indicate PAGF induces proliferation, activation antigens, and T3 expansion predominantly confined to the T4 subset in both CBC and PBL.
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PMID:Pregnancy-associated growth factor. I. A proliferative agent which expands adult and cord T4 cells in unfractionated cultures. 387 78

The majority of patients with Dermatitis Herpetiformis (DH) have a gluten-sensitive enteropathy which may be triggered by a T cell-mediated immune response to gluten. Using a proliferative assay, the responses to gluten fraction III, recall antigens and mitogens of peripheral blood mononuclear cells (PBMC) and gut T cell lines (TCL) isolated from patients with Dermatitis Herpetiformis (DH) and normal controls were studied. In most cases, neither PBMC nor gut T cell lines (which were predominantly CD3+, CD4+, TCR alpha beta +) from either controls or patients proliferated in response to gluten fraction III alone. However, the addition of 10 U/ml IL-2 to PBMC cultures containing gluten fraction III resulted in a marked increase in proliferation in 9/19 DH patients and 7/11 controls compared to IL-2 alone. Furthermore, gluten-induced upregulation of IL-2 receptor (CD25) expression was demonstrated on PBMC from 4/4 patients with DH and 2/3 controls after 7 days' culture with antigen. A similar effect by exogenous IL-2, or the same concentration of IL-4, was observed in 8/11 (P = 0.02) and 5/6 respectively DH, and 3/4 normal gut T cell lines. No difference was observed in the response of DH and control PBMC to Tetanus toxin, Candida albicans and PPD; both normal and DH gut T cell lines were unresponsive to these antigens. However, the addition of IL-2 increased the response to Candida albicans by DH gut T cell lines. Moreover, the response of DH gut T cell lines to PHA (P < 0.001), Concanavalin A and anti-CD3 were markedly reduced compared to PBMC from the same patients. These findings suggest that gluten-specific T cells present in the blood and gut of normal and DH individuals are activated by but do not proliferate in response to specific antigen.
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PMID:Lack of proliferative response by gluten-specific T cells in the blood and gut of patients with dermatitis herpetiformis. 749 50

Cytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL-2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN-gamma production from these cultures. The role that endogenous cytokines have on IFN-gamma induction was also studied. Addition of a neutralizing antibody to the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-gamma production. Neutralization of endogenous IL-15 also resulted in diminished IFN-gamma production from cultures stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4+ T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism of cytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator.
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PMID:Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15. 756 80


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