Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-2 (IL-2) was originally identified in 1976 as a growth factor for T lymphocytes. Since that time it has become an important mediator of immune function through its effects on the growth, development, and activity of T and B lymphocytes, natural killer cells, and lymphokine-activated killer cells. Only cells that bear a specific receptor for IL-2 respond to its immunoregulatory effects. Of all the lymphokine-receptor systems in immunology, perhaps most is known about the structure, function, and binding properties of IL-2 and its cognate receptor. There are two distinct, membrane-associated IL-2 binding components in the high-affinity IL-2 receptor: an alpha subunit and a beta subunit, which associate in a non-covalent manner. Each of these polypeptides can occur on the cell surface in the absence of the other and bind IL-2, although with only low or intermediate affinity relative to the high-affinity receptor complex. The primary structure of each chain has now been deduced from full-length cDNA. The rapid rate of association between IL-2 and the IL-2R alpha subunit is important in the formation of high-affinity binding sites, and the inducibility of the alpha gene contributes to the highly regulated and transient display of high-affinity IL-2R. The IL-2R beta chain controls the slow dissociation rate of IL-2 from the high-affinity receptor. Also, IL-2R beta appears centrally involved in internalization of IL-2 and signal transduction, functions mediated presumably through its long intracytoplasmic domain. However, the actual mechanism of signal transduction in the IL-2/IL-2R system remains undefined. IL-2R beta is a member of a novel family of cytokine-receptor proteins that includes receptors for IL-4, IL-6, and erythropoietin.
 ...
PMID:Interleukin-2 and the IL-2 receptor: new insights into structure and function. 169 45

The effects of an immunopotentiating drug, isoprinosine, on the splenocytes of BALB/c mice to produce cytokines were investigated. Isoprinosine enhanced IL-2 production, upregulating the expression of IL-2 receptor in vitro. It also significantly increased the IFN-gamma secretion and decreased the IL-4 production in vivo. The significance of these findings in terms of immune regulation is discussed.
 ...
PMID:Effect of isoprinosine on IL-2, IFN-gamma and IL-4 production in vivo and in vitro. 172 91

The authors measured plasma IL-1 (interleukin-1), IL-2, IL-2 receptor (IL-2R), IL-4, IL-6, tumor necrosis factor (TNF), and granulocyte macrophage colony stimulating factor (GMCSF) in 10 stable patients during hemodialysis (HD) using new or reused polyacrylonitrile (PAN) or cuprophan (CU) dialyzers. Five HD patients with wasting syndrome, and 16 normal controls, were included. Hemodialysis patients showed a marked elevation of IL-2R. No IL-4, IL-6, or GMCSF were detected in any group. Tumor necrosis factor and IL-2 in the HD group were comparable with control values. No difference was found in the TNF levels in HD patients with and without wasting syndrome. Cytokine levels were unaffected by either new or used PAN or CU dialyzers.
 ...
PMID:Cytokine levels during hemodialysis. 175 Dec 2

Nickel is the major cause of metal-induced allergic dermatitis. Twelve nickel-specific T cell clones were used to investigate the cellular immune reactions occurring in nickel sensitivity. The selection between the alternative T cell receptors alpha beta and gamma delta and two alternative V beta genes (V beta 5 and V beta 8) were studied to see if nickel induces a selective pressure for clones bearing particular genes. Cell surface markers were studied by monoclonal antibodies and flow cytometry. Soluble mediators were measured by an ELISA method. The clones used T cell receptor alpha beta genes but did not use V beta 5 or V beta 8. They were T helper clones with a primed memory marker (CD3+ CD4+ CD8- CD45RO+) and carried HLA-DR. None of the clones secreted IL-1 alpha, all of them secreted IL-2 receptor. Four clones secreted IL-1 beta, six IL-4 and seven IL-6, the peaks in IL-2R and IL-6 secretion preceding IL-4 secretion. The clones helped immunoglobulin synthesis. The clones from late effector phase of the nickel allergic reaction favours the use of T cell receptors alpha beta genes. Nickel-specific clones were phenotypically indistinguishable but differed in soluble mediators produced.
 ...
PMID:Characterization of nickel-specific T cell clones. 182 95

The aim of the present work was to study regulatory interactions between MHC class I molecules and the interleukin (IL)-2, IL-3, and IL-4 receptors and functional interactions between the receptors for IL-2 and IL-4. Our major observations were: (1) quiescent splenic T cells exposed to specific anti-MHC class I antibodies become responsive to IL-2 and IL-4 stimulation; (2) T-cell clones (CTLL-2 and HT-1) grown at high cell density or low IL-2 concentrations become refractory to IL-2 and IL-4 stimulation. After exposure to anti-class I antibodies the refractory cells recover responsiveness to lymphokine-induced proliferation; (3) IL-2 receptor expression is non-inducible in class I-negative T-lymphoma cells, but is inducible following class I gene transfection of the cells; (4) exposure of T-cells and clones to IL-2 receptor antibody increases the responsiveness to IL-4 stimulation; (5) IL-2 and IL-4 act synergistically at low and substimulatory lymphokine levels; and (6) IL-3 responsiveness of hemopoietic cells is not influenced by exposure to anti-MHC class I antibody. It is concluded that class I molecules are of importance for the functional expression of the receptors for IL-2 and IL-4 and that these receptors are functionally interrelated.
 ...
PMID:T-cell activation. IV. Evidence for a functional linkage between MHC class I, interleukin-2 receptor, and interleukin-4 receptor molecules. 183 52

In this present study, lymphokine (IL-2/IL-4) production in VSV-induced Th cell (L3T4+Lyt-2- VSV-immune T cells) and memory CTL populations (L3T4-Lyt-2+ VSV-immune T cells) has been assessed in order to gain some understanding as to why the Lyt-2+ subset (L3T4-independent Th cell pathway) fails to provide Th cell function for anti-VSV CTL responses. Our studies demonstrated that following specific antigen (VSV, H-2 antigen) or mitogen stimulation, lymphokine activity was detected in the supernatants obtained from VSV-induced Th but not VSV memory CTL populations. The presence of blocking concentrations of PC61, a monoclonal antibody (mAb) to the IL-2 receptor (IL-2R), revealed augmented lymphokine activity only in the VSV-induced Th cell supernatant. VSV-induced Th cells secreted both IL-2 and IL-4 following stimulation with VSV. Two lines of evidence supported the view that both these lymphokines were important for an anti-VSV CTL response: (1) mAb to either IL-2 or IL-4 inhibited CTL maturation and (2) the combination of exogenous IL-2 and IL-4 reconstituted a class I-restricted. VSV-specific CTL response in Th cell-depleted T cell cultures. The failure to detect lymphokine production in bulk cultures of the VSV memory CTL population was consistent with limiting dilution (LD) analysis of lymphokine-producing cells in the spleen of VSV-immune mice. Thus, approximately 1/15,000 Lyt-2-depleted, VSV-immune T cells were positive for lymphokine production following VSV stimulation, whereas less than 1/1,000,000 L3T4-depleted, VSV-immune T cells were scored as lymphokine-secreting cells following stimulation with this same virus. Similarly, precursor estimates for lymphokine-producing cells against allogeneic class I antigens demonstrated that the majority of lymphokine-producing cells also resided in the L3T4+ subset. Lymphokine-secreting Lyt-2+ cells were detected at low but not high cell densities suggesting that Lyt-2+ cells may secrete another lymphokine(s) that inhibits IL-2/IL-4 production. Thus, these studies demonstrate an obligatory requirement for the L3T4-dependent Th cell pathway for optimal CTL responses derived from either CTLp or memory CTLs.
 ...
PMID:T helper cells in cytotoxic T lymphocyte development: analysis of the cellular basis for deficient T helper cell function in the L3T4-independent T helper cell pathway. 185 Jun 63

The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non-allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed.
 ...
PMID:Serum levels of soluble IL-2 receptor, IL-4 and IgE-binding factors in childhood allergic diseases. 186 9

We have used the technique of in situ hybridization to investigate the transcription of genes encoding the CD3 complex and the lymphokine interleukin 4 (IL-4) by human pro-T cells--i.e., cells that phenotypically resemble those T-cell precursors that colonize the thymus during early intrathymic development. CD1-2-3-4-7+8-45+ pro-T cells isolated from postnatal thymi via immunoselection with a panel of specific monoclonal antibodies are already committed to the T-cell lineage because most of them transcribe the genes encoding the delta and epsilon chains of the CD3 complex. About half of such pro-T cells synthesize IL-4 mRNA in the absence of any exogenous stimulation. Upon culture with IL-4, pro-T cells extensively proliferate and differentiate into functionally competent, mature gamma delta T cells expressing a T-cell receptor repertoire similar to that of gamma delta T cells that can be found in postnatal thymus. The IL-4 response of pro-T cells is not mediated by induction of the interleukin 2 (IL-2)-IL-2 receptor pathway and, unlike IL-2-driven T-cell differentiation, does not require the presence of stromal cells. Taken altogether, these findings suggest that an autocrine IL-4-mediated pathway might be implicated in early thymocyte differentiation--namely, in the generation of T cells bearing the gamma delta T-cell receptor.
 ...
PMID:Involvement of the interleukin 4 pathway in the generation of functional gamma delta T cells from human pro-T cells. 188 11

We examined the effects of interleukin 4 (IL-4) on the expression of IL-2 receptor p75 (IL-2R p75) or beta chain on various human T cells. IL-4 promptly down-regulated surface IL-2 receptor (IL-2R) p75 in these cells. Although IL-2-induced IL-2R p75 down-regulation was seen more quickly, IL-2 did not contribute to the process of the IL-4-induced decrease of IL-2R p75. Northern blotting revealed that IL-4 did not reduce the expression of IL-2R p75 mRNA. Studies using Pronase E, which digests cell surface IL-2R p75, or brefeldin A, which blocks intracytoplasmic protein transport from endoplasmic reticulum to the Golgi apparatus, suggest that IL-4-induced IL-2R p75 down-regulation is controlled after IL-2R p75 is expressed on the cell surface. We found that IL-4 accelerated the endocytosis of IL-2R p75, which was monitored by [125I]Mik-beta 3 monoclonal antibody that recognizes non-IL-2-binding epitope on IL-2R p75. These findings demonstrate that IL-4 down-regulates IL-2R p75 mainly by accelerating its endocytosis.
 ...
PMID:IL-4 down-regulates IL-2 receptor p75 by accelerating its endocytosis. 188 7

Previous work indicated that a CTL response can be generated by the combination of IL-2 plus IL-6 or IL-4 alone. Because of the ubiquitous production of IL-6 and its apparent ability to induce IL-2, we explored the interdependence of these lymphokines in supporting a CTL response from murine thymocytes. For thymocytes cultured in IL-4, further addition of IL-6 enhanced thymocyte proliferation. In addition, a role for IL-6 in thymocyte activation was indicated by the ability of anti-IL-6 mAb to block both IL-4-directed proliferation and the cytotoxic response found in the presence of IL-4. The addition of IL-2 to limiting doses of IL-4 augmented the CTL response; however, the response to high levels of IL-4 was not augmented by addition of IL-2. Consistent with this apparent involvement of IL-2 in the IL-4-mediated response we found: (a) that mAb to IL-2 significantly reduced the CTL response generated in the presence of IL-4; (b) that IL-2 activity was present in culture supernatant following incubation of thymocytes with high levels of IL-4; and (c) that enhanced IL-2 receptor expression found in the presence of IL-4 was blocked with the addition of anti-IL-2 antibody to the thymocyte culture. In contrast to the data for proliferation, anti-IL-4 mAb had no effect on the generation of CTL in the presence of IL-2 + IL-6 but readily blocked the CTL response to IL-4. These results indicate that, for thymocyte responders, the CD8+ CTL generated in the presence of IL-4 require both IL-2 and IL-6.
 ...
PMID:IL-4-supported induction of cytolytic T lymphocytes requires IL-2 and IL-6. 190 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>