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)

The arotinoid temarotene (Ro 15-0778) and its metabolite Ro 14-6113 were examined in a variety of in vitro assays quantitating parameters of human immune functions. Both immunosuppressive and immunostimulatory activities of these compounds were identified. These activities were compared with those of the known immunomodulatory compound ciclosporin A (CsA) at concentrations corresponding to clinically effective plasma concentrations. Like CsA, Ro 14-6113 inhibited the mitogen- or alloantigen-induced proliferation of T cells as well as their capacity to secrete interleukin-2 (IL-2), interferon-gamma and tumor necrosis factor alpha. Ro 15-0778 showed no activity in inhibiting cytokine secretion and was considerably less effective than Ro 14-6113 in inhibiting T cell proliferation. Ro 14-6113 was more effective than CsA in inhibiting IL-2 receptor expression. Ro 14-6113 modulated both positively or negatively the proliferation of B cells, depending on the concentration. Ro 14-6113 inhibited the secretion of IgM, IgG, and IgA, while stimulating IgE secretion. A different profile of activity for Ro 14-6113 and CsA was observed, suggesting differing effectiveness in immunologically mediated diseases.
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PMID:Modulation of human immune functions in vitro by temarotene and its metabolite. 183 65

Lymphocytes from osteopetrotic (op) rats, compared to their normal (n) littermates, exhibit defective immune functions associated with their inability to resorb bone. Among these immune defects are the failure of their spleen cells to proliferate normally to mitogens and to generate IL-2. Addition of exogenous IL-2 failed to reverse the suppressed proliferation in the op spleen cells, indicating that additional defects were involved in the suppression. Phenotypic analysis of cellular constituents of op and n spleens revealed that the percentages of T cells, macrophages, and IL-2 receptor positive cells were not different. Furthermore, there was no difference in CD4 (W3/25) and CD8 (OX8) cells. However, the Ia+ (OX3) cells in the op spleen represented less than 50% of those found in the n spleen, but the op had higher levels of transferrin receptor (OX26). On the basis of the ability of interferon-gamma (IFN-gamma) to increase Ia expression, this cytokine was added to op spleen cells (10-50 U/ml) and found to increase the number of Ia+ cells to the level found in n spleen cells. Moreover, pretreatment of op spleen cells with IFN-gamma restored their ability to proliferate to mitogens and their responsiveness to IL-2. Not only did IFN-gamma reverse the defective response to IL-2, but it also augmented the defective IL-2 production by op spleen cells. Taken together, these findings demonstrate that IFN-gamma can reverse many of the impaired immune functions characteristic of op spleen cells in vitro. Furthermore, these data suggest that IFN-gamma may provide an important avenue of treatment in these animals that may contribute to restoration of normal bone resorption.
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PMID:Reversal of immune dysfunction in osteopetrotic rats by interferon-gamma: augmentation of macrophage Ia expression and lymphocyte interleukin-2 production and proliferation. 190 14

Adherent lymphokine-activated killer cells (A-LAK) are highly potent cytotoxic cells, which are shown to be derived not only from natural killer (NK)/K cells but phenotypically also from T cells. The generation and phenotypical and functional characterisation of these T-cell-derived A-LAK are described. In contrast to non-adherent cells (NA-LAK) and unseparated LAK (UN-LAK), these mostly CD3+ CD56+ CD8+ cells display a high degree of expansion following initial interleukin-2 (rIL-2) activation and further culturing in autologous conditioned medium. A comparison of cytotoxic activities of cultured cells reveals a significantly higher oncolytic ability of A-LAK cells against both K562 and Daudi cells than that of cultured controls of NA-LAK and UN-LAK. In addition, A-LAK are characterised by a marked endogenous cytokine release of interferon gamma, tumour necrosis factor alpha and IL-6 as well as by their shedding of p55 IL-2 receptor after exposure to IL-2. The results demonstrate A-LAK to be the lymphocyte subpopulation with the most cytotoxic activity and endogenous cytokine release after exposure to IL-2. The improvement of techniques for long-term cultures may be of interest for future therapeutic approaches.
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PMID:High release of tumor necrosis factor alpha, interferon gamma and interleukin-6 by adherent lymphokine-activated killer cells phenotypically derived from T cells. 190 99

The effect of recombinant interleukin 2 (IL-2) and IL-4, as well as a combination of both lymphokines on human post-natal thymocytes at different maturation stages, was analyzed by culturing highly purified pro-T cells, pre-T cells, double-negative and double-positive thymocyte subsets in the presence of IL-2 and/or IL-4. Both IL-2 and IL-4 responsiveness are developmentally regulated in human thymocytes, since IL-2 and IL-4 responses decline with increasing thymocyte differentiation, double-positive T cells displaying far less proliferation than immature thymocytes. IL-2 and IL-4 may influence pro-T cell growth in both an antagonistic and additive fashion. At low doses, IL-4 inhibits IL-2-supported growth of pro-T cells, whereas, at higher concentrations, this inhibitory effect is masked by the ability of IL-4 to stimulate pro-T cell proliferation. In contrast to peripheral lymphocytes, IL-4 does not down-regulate the expression of the IL-2 receptor light chain on thymocytes. In pro-T cell cultures, IL-2 and IL-4 favour the differentiation of distinct cell populations, namely lymphocytes displaying preferentially a TCR alpha/beta+ and CD4+CD8- phenotype versus predominantly TCR gamma/delta+ and CD4-CD8+ cells, respectively. The effect of IL-2 dominates over that of IL-4, since the composition of cultures set up in the presence of IL-2 plus IL-4 resembles that of cells cultured with IL-2 alone. In synthesis, IL-2 and IL-4 exhibit reciprocal inter-relations in human thymocyte cultures, thus supporting the notion that these lymphokines are implicated in the complex regulation of a local cytokine network.
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PMID:Interplay between IL-2 and IL-4 in human thymocyte differentiation: antagonism or agonism. 191 31

Recent studies have identified a new family of cytokine receptors, which is primarily characterized by the conservation of periodically interspersed four cysteine residues and the W-S-X-W-S sequence ('WS motif') within the extracellular domain. However, the role of such conserved structures still remains elusive, in particular that of the WS motif. Interleukin-2 (IL-2) is known to play a critical role in the clonal expansion of antigen-stimulated T lymphocytes, and the IL-2 signal is delivered by one of the receptor components, the IL-2 receptor beta (IL-2R beta) chain. The IL-2R beta chain, unlike the IL-2R alpha chain, belongs to this receptor family. In the present study, we analyzed the function of the WS motif of IL-2R beta (Trp194-Ser195-Pro196-Trp197-Ser198) with the use of site-directed mutagenesis. Our results indicate the critical role of the two Trp residues in the proper folding of the IL-2R beta extracellular domain and point to the general functional importance of the WS motif in the new cytokine receptor family.
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PMID:The integrity of the conserved 'WS motif' common to IL-2 and other cytokine receptors is essential for ligand binding and signal transduction. 191 91

Soluble CD8, soluble CD4, soluble CD25 (IL-2 receptor), beta 2-microglobulin and the cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in sera from patients with common variable immunodeficiency (CVI). Levels of soluble CD8, soluble CD25 and beta 2-microglobulin but not of soluble CD4 and TNF-alpha were raised significantly above levels in normal sera. Sera from patients with X-linked agammaglobulinaemia, who are also antibody deficient, did not show this marked elevation. The raised levels of soluble CD8, soluble CD25 and beta 2-microglobulin in CVI, correlated with the extent of the defects in the B lymphocytes assessed in vitro, as well as with the clinical severity of the disease. The selective release of these molecules into sera may indicate that abnormal cellular activation occurs in most CVI patients. It is also possible that the raised levels of these soluble molecules play a part in the immunodeficiency.
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PMID:Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency. 193 93

Serum levels of the cytokines interleukin-1 alpha (IL-I alpha), IL-1 beta, IL-2, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha) and the soluble IL-2 receptor were measured in chronic progressive multiple sclerosis patients (CPMS) and normal, inflammatory, and noninflammatory disease controls. Serum IL-2 levels displayed the most consistent abnormalities in the group of tests for the CPMS group, and were the only cytokine levels to achieve significance in statistical group analyses. However, several patients with CPMS had normal serum IL-2 levels. An incidental finding was a statistical correlation between serum IL-2 and TNF-alpha levels among all groups tested. This finding was supported on analysis of serial serum samples from CPMS patients. These results suggest a linkage of IL-2 and TNF-alpha production, especially in pathological conditions.
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PMID:Serum cytokine levels in chronic progressive multiple sclerosis: interleukin-2 levels parallel tumor necrosis factor-alpha levels. 205 69

The regulation of rat lymphokine-activated killer (LAK) cell generation from their purified precursors using various cytokines was studied. Several important findings emerged from this study. These include: (i) interleukin-2 (IL-2), but not any other cytokine tested, is pivotal for the development of LAK cells; (ii) transforming growth factor beta 1 (TGF-beta) inhibits IL-2-induced LAK cell differentiation, but not proliferation, regardless of the dose of IL-2 used; (iii) interferon-gamma (IFN-alpha) is inhibitory for LAK cell proliferation, but not differentiation; (iv) tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma synergize with a low but not a high concentration of IL-2; (v) TNF-alpha reverses the anti-differentiative activity of TGF-beta 1 in the presence of a high, but not a low, concentration of IL-2; (vi) anti-p55 IL-2 receptor (R) is not inhibitory for LAK cell development but, on the contrary, a low concentration of this antibody synergizes with IL-2; (vii) IL-1 alpha, IL-1 beta, IL-3, IL-4, IL-6, IFN-alpha. TNF-alpha, or TGF-beta 1 do not affect LAK cell function; and (viii) IL-2 may provide two separate signals for LAK precursors: one is proliferative and the other is differentiative.
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PMID:Differential effects of various cytokines on the generation of rat LAK cells from their purified precursors. 211 78

Lymphokine-dependent T cell proliferation is regulated in part by the cell surface expression of high affinity interleukin-2 receptors (IL-2R). The functional, high affinity form of the IL-2 receptor is comprised of two ligand binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). In the absence of the other subunit, IL-2R alpha and IL-2R beta bind ligand with only low or intermediate affinity, respectively. The inducible and transient expression of IL-2R alpha regulates the display of high affinity receptors, while IL-2R beta appears to contribute importantly to growth signal transduction. Although the primary structure of both receptor chains has now been elucidated, the mechanism of growth signal transduction through the high affinity IL-2R remains undefined. Of note, IL-2R beta belongs to a novel family of cytokine receptors including the binding proteins for IL-3, IL-4, IL-6, erythropoietin, and granulocyte-macrophage colony-stimulating factor. These various receptors may well utilize a common intracellular signalling pathway.
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PMID:The human interleukin-2 receptor: insights into subunit structure and growth signal transduction. 212 4

In addition to the regulation of B lymphocyte growth and differentiation, the cytokine IL-4 (BSF-1) exerts effects on T lymphocytes and other bone marrow-derived lineages. We show here that recombinant mouse IL-4 synergizes with low levels of IL-2 to increase the yield of cytotoxic activity in a primary MLR, and the proliferation of both cloned IL-2-dependent CTL lines and cells obtained from a primary MLR. IL-4 did not induce the proliferation of any of several cloned CTL cell lines on its own. It also did not replace IL-2 in stimulating the growth or reactivation of quiescent, antigen-dependent CTL clones. However, IL-4 was synergistic with IL-2 after reactivation of the quiescent cells with antigen plus IL-2. Enhancement by IL-4 of the IL-2-driven proliferation of an antigen-independent line was blocked by the addition of anti-IL-4 monoclonal antibody. Although incubation of the CTL clones with IL-4 or with IL-2 plus IL-4 induced a transient increase in the expression of the mRNA encoding the 55 kDa IL-2 receptor, no change in the number or affinity of IL-2 receptors because of IL-4 was detected. This suggests that IL-4 does not potentiate the IL-2 response by altering IL-2 receptor levels. Instead, we propose that the synergistic effect of IL-4 is mediated by a different signalling mechanism from that used by IL-2.
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PMID:IL-4 potentiates the IL-2-dependent proliferation of mouse cytotoxic T cells. 213 90


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