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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 have examined the mechanisms of 1,25-dihydroxyvitamin D3 (D3)-mediated inhibition of human B cell differentiation to immunoglobulin (Ig) secreting cells. B lymphocytes were purified from human tonsils and peripheral blood mononuclear cells. Mononuclear cells were separated into adherent cells and nonadherent cells. Cells were stimulated with Staphylococcus aureus Cowen I (SAC) or pokeweed mitogen (PWM) for 7 days and immunoglobulin production was measured by ELISA assay, 1,25-dihydroxyvitamin D3 was added at different times during cultures. 1,25-Dihydroxyvitamin D3, in a dose-dependent manner, inhibited both SAC and PWM-induced Ig production by mononuclear cells. The maximum inhibition was observed when 1,25-dihydroxyvitamin D3 was added at the beginning of culture, but inhibition could still be observed when 1,25-dihydroxyvitamin D3 was added on day 4 of cultures. The inhibitory effect of 1,25-dihydroxyvitamin D3 on Ig production was significantly greater on mononuclear cells than on nonadherent cells. Addition of in vitro purified IL-1 to nonadherent cells enhanced 1,25-dihydroxyvitamin D3-induced inhibition of Ig production. 1,25-Dihydroxyvitamin D3 also inhibited the expression of IL-2 receptors on B cells activated with SAC. 1,25-dihydroxyvitamin D3 did not inhibit Ig production by SAC preactivated B cell blasts in response to T cell supernatants. These data suggest that vitamin D3 inhibits Ig production by inhibiting IL-2 receptor expression on B cells and via its effect on adherent macrophages. Vitamin D3 does not influence the effect of differentiation factors on activated B cells that have already expressed growth/differentiation factor receptors.
Clin Exp Immunol 1987 Sep
PMID:1,25-Dihydroxyvitamin D3-mediated inhibition of human B cell differentiation. 311 62

It has previously been demonstrated that retinoic acid (RA) enhances the blastogenic responses of human thymocytes. We have now delineated the cellular mechanism of this activity. When RA was added to resting thymocyte cultures in the presence of recombinant interleukin-2 (rIL-2), blastogenesis was increased two- to fourfold. By assessing the proportion of cells that became Tac-positive and showed DNA synthesis early in the activation process, we determined that the augmentation by RA was not caused by an increased recruitment of resting cells that are activated to undergo blast transformation. Instead, RA markedly potentiated the growth rate of long-term rIL-2-dependent thymocyte blasts and, correspondingly, increased the Tac expression on these proliferating cells. Thus, RA enhancement of thymocyte responses appears to be mediated by an increase in IL-2-receptor expression on thymocyte blasts, resulting in augmented IL-2-dependent growth. This effect is independent of the original activating stimulus since enhancement of thymocyte responses to phytohemagglutinin (PHA) was also shown to be caused solely by increased proliferation of IL-2-dependent blast growth. In contrast to these effects on thymocytes, peripheral blood lymphocyte (PBL) proliferative responses were unaffected by RA treatment and, correspondingly, RA affected neither IL-2 receptor expression on PBL blasts nor the growth of these cells. Taken together, the results of this study suggest that RA can modulate IL-2-dependent immune responses, in part, by upregulating the expression of IL-2 receptors on proliferating T lymphoblasts generated from cells at restricted stages of development.
Cell Immunol 1988 Sep
PMID:Retinoic acid upregulates interleukin-2 receptors on activated human thymocytes. 313 32

We studied the effect of highly purified recombinant interleukin 2 from Escherichia coli (rIL-2) on antibody production by our human hybridomas. Increasing concentrations of rIL-2 were directly related to increased production of immunoglobulin, which reached peak levels of 13-25 micrograms/ml, a 10- to 20-fold increase over untreated hybridomas. We were unable to demonstrate large quantities of the IL-2 receptor on the hybridomas as measured by an anti-TAC monoclonal antibody. The data suggest that the antibody enhancement phenomenon is mediated by IL-2 and that is a new, effective way to achieve higher levels of immunoglobulin from human hybridomas.
Cell Immunol 1988 Sep
PMID:Recombinant human interleukin 2 (rIL-2) enhancement of antibody production by human-human hybridomas. 313 33

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.
J Clin Oncol 1988 Sep
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

We report here the results of in vitro studies that demonstrate that purified human recombinant interleukin-2 (hrIL-2) is a potent stimulant for freshly isolated cord blood lymphocytes of healthy full-term infants. Different culture parameters were studied to define the optimal conditions for eliciting maximal levels of activation. Highest levels of hrIL-2-induced TdR[3H] uptake were recorded on day 7 for cultures containing 100 U hrIL-2/ml. Results of comparative studies demonstrated that the reactivity of cord blood lymphocytes to hrIL-2 was equal to, if not greater than, that of healthy adult lymphocytes. Cord blood cells that had been activated with hrIL-2 could be propagated in long-term (greater than 30 days) cultures as hrIL-2-dependent lines, and these lines could be initiated with a high degree of success. Phenotypic analysis was performed using different monoclonal antibodies and cytofluorometry, and studies characterizing cells of the long-term lines have shown that they consisted of a heterogenous population of T4 helper and T8 cytotoxic/suppressor cells; in some instances, natural killer (NK) cells were also present. Other experiments demonstrated that hrIL-2-activated and hrIL-2-propagated T cells expressed the IL-2 receptor (IL-2R; defined by monoclonal antibody anti-Tac) and the number of IL-2-R-positive cells could be increased two-fold or more by exposing the cells to a phorbol ester. This report provides additional information to support the hypothesis that hrIL-2 not only sustains T cell proliferation (i.e., second signal) but also induces T cell activation (i.e., first signal).(ABSTRACT TRUNCATED AT 250 WORDS)
J Clin Lab Immunol 1987 Sep
PMID:Activation and long-term proliferation of human cord blood T cells with human recombinant interleukin-2. 350 Mar 15

To investigate the immune defect in lepromatous leprosy we studied immune cell phenotypes, lymphocyte activation states, and interleukin-2 (IL-2) production in naturally occurring leprosy skin lesions. Mouse hybridoma monoclonal antibodies reacting with the IL-2 receptor (anti-Tac), unbound IL-2 (DMS-1), antigen-presenting Langerhans' cells (OKT6) and the OKT4-Leu3 and OKT8 T-lymphocyte subpopulations were used with indirect horseradish peroxidase and alkaline phosphatase techniques on frozen biopsy sections. The percentage of Tac+ lymphocytes and the number of OKT6+ cells in the epidermis and dermal granuloma were significantly correlated in naturally occurring lesions (correlation coefficient 0.79) and were higher in tuberculoid than in lepromatous lesions. Leu3 antigen was expressed by 70-90% of Tac+ cells in tuberculoid lesions. Although the percentage of cells producing IL-2 was low in lesions of both lepromatous and tuberculoid patients, it was about 15 times greater in tuberculoid than in lepromatous lesions (0.032 +/- 0.037 tuberculoid vs 0.0019 +/- 0.023 lepromatous). There was an association between the number of OKT6+ cells and the percentage of IL-2-producing cells, but the association was weaker than that of OKT6+ cells and the percentage of IL-2 receptor-bearing cells (r = 0.2), implying that IL-2 production is not an intervening variable in the latter association. The absolute number of OKT4-Leu3+ lymphocytes was significantly different in different clinical leprosy groups and was positively correlated with host resistance (mean OKT4-Leu3+ cells/mm2 in 6 micron sections; 1412 +/- 288 tuberculoid, 400 +/- 93 borderline lepromatous, 200 +/- 100 polar lepromatous; r = 0.95). Absolute numbers of OKT8+ cells/mm2 in lesions were not significantly different. We conclude that there is a relative paucity of OKT4-Leu3+ cells as well as IL-2-producing cells at the local level in lepromatous leprosy lesions. Possible functional relationships between these findings and the failure of macrophage activation and destruction of Mycobacterium leprae in lepromatous leprosy are discussed.
Int J Lepr Other Mycobact Dis 1985 Sep
PMID:In vivo responses to Mycobacterium leprae: antigen presentation, interleukin-2 production, and immune cell phenotypes in naturally occurring leprosy lesions. 390 Feb 45

Concanavalin A (Con A), cloned interleukin 2 (IL-2), purified interleukin 1 (IL-1) or two different crude preparations containing IL-1 activity alone, did not induce proliferation of rigorously accessory cell (AC)-depleted splenic L3T4+ or Lyt 2+ lymphocytes. Con A together with saturating concentrations of cloned IL-2 (100 U/ml) promoted less than 40% of the proliferative responses observed in AC-supplemented L3T4+ and Lyt 2+ T-cell cultures. The three preparations of IL-1 used supported minimal proliferation of Con A-treated purified L3T4+ or Lyt 2+ lymphocytes. However, all these IL-1 preparations promoted significant growth of the T-cell populations if AC (1%) were included in the cultures. Cloned IL-2 combined with purified IL-1 promoted proliferation of Con A-treated L3T4+ and Lyt 2+ lymphocytes achieving approximately 75% of the responses observed in AC-supplemented T-cell cultures. The additive effect of IL-1 was apparent in the presence of saturating concentrations of cloned IL-2. Finally, Con A alone induced a detectable number of both L3T4+ and Lyt 2+ lymphocytes to express IL-2 receptors as determined with the anti-mouse IL-2 receptor antibody 7D4 by immunofluorescence and FACS analysis. Purified IL-1 neither induced detectable number of L3T4+ or Lyt 2+ T cells to express IL-2 receptors nor increased the number of Con A-treated T cells bearing IL-2 receptors. We have interpreted these findings to indicate the following: Con A alone is sufficient to induce highly purified L3T4+ and Lyt 2+ lymphocytes to express IL-2 receptors. Cloned IL-2 and purified IL-1 are required for optimal growth of L3T4+ and Lyt 2+ lymphocytes and these cytokines together efficiently replace AC in growth of T cells initiated by Con A. IL-1 alone does not replace AC in Con A-induced activation of mouse T cells. IL-1 exerts potentiation on IL-2-driven growth of Con A-treated L3T4+ and Lyt 2+ lymphocytes. The additive activity of IL-1 on growth of normal T cells is not due to increased production of IL-2 in the cultures or induction of normal T cells to expression of IL-2 receptors by IL-1. We propose that IL-1 optimizes the action and/or interaction of IL-2 with its receptors on the T-cell membrane (by, i.e., increasing affinity of the IL-2 receptor for its ligand and/or stabilizing the IL-2 receptor).
Cell Immunol 1985 Sep
PMID:Both cloned interleukin 2 and purified interleukin 1 are required for optimal growth of purified L3T4+ and Lyt 2+ lymphocytes initiated by concanavalin A. 392 71

Gamma interferon induced surface expression of interleukin 2 (IL-2) receptors on normal human monocytes and the monocytoid cell lines U937 and HL60. These receptors were detected by anti-IL-2 receptor monoclonal antibodies, and U937 IL-2 receptors were indistinguishable from T lymphocyte IL-2 receptors by immunoprecipitation. Also, U937 IL-2 receptors bound biologically active IL-2. These results suggest a role for monocyte IL-2 receptors in T cell/monocyte interaction during an immune response.
J Exp Med 1985 Sep 01
PMID:Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells. 392 3

We have used cDNAs for the human interleukin 2 (IL-2) receptor to study IL-2 receptor gene expression in normal activated T cells. Resting T cells do not contain detectable IL-2 receptor mRNA. Within 1 hr after stimulation with phytohemagglutinin (PHA), a large, presumably nuclear precursor RNA species is seen, which then gradually disappears. Mature IL-2 receptor mRNA forms appear within 8 hr after stimulation, reach peak levels between 8 and 24 hr, and then decline. Thus, in PHA-activated lymphocytes the rise and fall in IL-2 receptor mRNA levels precede by more than 24 hr the peak and decline of IL-2 receptor protein expression occurring at the cell surface. 4 beta-Phorbol 12-myristate 13-acetate (PMA) also stimulates IL-2 receptor mRNA and protein expression by T cells. Combinations of optimal concentrations of PHA and PMA produce an additive effect on IL-2 receptor mRNA levels, suggesting that PHA and PMA may induce IL-2 receptor gene expression through different, complementary mechanisms. Nuclease S1-protection assays indicate that IL-2 receptor mRNAs may differ in length due to the use of three different polyadenylylation signals. Further, these assays demonstrate the presence of transcripts that lack a 216-base segment within the protein-coding region and thus do not encode a functional IL-2 receptor. Nuclear transcription assays indicate that the increase in IL-2 receptor mRNA is reflected at the level of transcription. Thus, IL-2 receptor gene regulation controls IL-2 receptor expression at the cell surface and is intimately linked to the control of T-cell proliferation.
Proc Natl Acad Sci U S A 1985 Sep
PMID:Interleukin 2 receptor gene expression in normal human T lymphocytes. 392 55

The two compounds, the calcium ionophore A23187 and phorbol myristate acetate (PMA), which are not mitogenic for mouse thymocytes, induce proliferation when added in combination to thymocyte cultures. Short exposure to PMA renders the cells responsive to IL-2, added exogeneously. The cells rendered IL-2-responsive by PMA are enriched in the more mature peanut agglutinin (PNA)-negative population. The ionophore does not render PNA-negative thymocytes IL-2-responsive, but induces proliferation of PMA-pulsed PNA-negative thymocytes. PMA-pulsed PNA-negative thymocytes proliferating in response to either exogeneous IL-2 or ionophore express IL-2 receptors. However, the ionophore does not mimic IL-2 action but acts indirectly by induction of both IL-2 production and of IL-2 receptor expression via IL-2. This view is based on the following findings: 1) IL-2 could be detected in supernatants derived from PMA-preactivated thymocytes incubated with the ionophore; 2) The IL-2-induced proliferation, as well as the ionophore-induced proliferation, was specifically blocked by a monoclonal anti-IL-2-receptor antibody; 3) The proliferation induced by exogeneous IL-2, as well as that induced by the ionophore, could be specifically inhibited by metabolically blocked T lymphoblasts carrying IL-2 receptors competing with the responder cells for the available IL-2 added or produced in the system.
Immunobiology 1985 Sep
PMID:The mode of action of the calcium ionophore A23187 on T cell proliferation. I. The ionophore does not replace lymphokines but acts via induction of IL-2 production on IL-2 responsive cells. 393 89


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