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

For successful allogenic pregnancy to occur, suppression of maternal defense responses toward the fetus are vital. Suppressor factors elaborated by decidual cells or immune cells may facilitate this suppression. In order for appropriate cellular responses to occur an intact signal transduction/second messenger system must be present. The calcium/phospholipid-dependent protein kinase, Pk-C, plays an important role in regulating immune responses, and may also be important in regulating uterine cell responses and implantation events. Pk-C activation is necessary for IL-2 synthesis and IL-2 receptor synthesis through activation of the proto-oncogenes c-jun and c-fos. These proto-oncogene gene products combine to form the heterodimer AP-1 which then activates IL-2 gene transcription for both peptide and receptor. If Pk-C activity becomes abrogated then appropriate cell responsiveness is diminished. We have shown that Pk-C activity is decreased in the particulate fraction of 4-7 day pregnant spleen, thymus and draining lymph node (DLN) cells. Spleen cells did not exhibit any change in cytosolic Pk-C activity, the thymus was found to have a decrease in both cytosol and particulate fractions, and the DLN cells exhibited a translocation effect whereby particulate Pk-C decreased and cytosolic Pk-C activity increased. Supernatant from 3-day cultures of DLN cells from pregnant animals was shown to inhibit proliferation of spleen cells. In addition, the supernatant was able to directly lower Pk-C activity. We hypothesize that DLN cells secrete a factor(s) that is able to suppress immune response through abrogation of Pk-C activity, thereby decreasing AP-1 formation resulting in decreased IL-2 synthesis and IL-2 receptor synthesis.
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PMID:Pregnancy-associated, lymphocyte-derived suppressor factor inhibits protein kinase C activity. 822 96

Previous studies established that low in vitro temperatures (27 degrees C, termed nonpermissive) suppressed murine primary thymus-dependent (TD), but not primary thymus-independent (TI) or secondary TD, antibody responses. Suppression was rescued by the addition of oleic acid (18:1), recombinant interleukin (rIL)-2 and/or rIL-4, but not rIL-1. These observations suggested that low temperatures suppress the functions of virgin T cells (Tv) but not those of memory T cells (Tm), B cells, or accessory cells and that hypothetically 18:1 may rescue suppressed responses by altering the membranes of Tv cells, allowing them to proliferate and subsequently secrete interleukins. In this study negatively selected Tm and Tv cells were stimulated with various mitogens at 37 or 27 degrees C. The results indicated that proliferation was suppressed at 27 degrees C to all mitogens tested. The subsequent addition of 18:1 induced proliferative responses at 27 degrees C to both concanavalin A (Con A) and a combination of 12-O-tetradecanoylphorbol 13-acetate (TPA) and calcium ionophore (A23187), but not to phytohemagglutinin-P (PHA). Both Tm and Tv cells showed significant secretion of IL-2 and expression of IL-2 receptor (IL-2R) at 27 degrees C in response to all mitogens, irrespective of proliferation, and the subsequent addition of 18:1 caused little or no change in the levels of IL-2 secretion or IL-2R expression. These findings indicate that suppression of Tm and Tv cell proliferative responses occurs irrespective of IL-2R expression and, unlike antibody production, of IL-2 secretion. Furthermore, it appears that 18:1 can synergistically act with Con A or TPA/A23187, but not PHA, in activating Tm and Tv cells to induce proliferation at 27 degrees C. These findings suggest differences in signal transduction mechanisms between these various mitogens.
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PMID:The effects of temperature and oleic acid on murine memory and virgin T cell activation: interleukin-2 secretion and interleukin-2 receptor expression. 824 70

A detailed analysis of the immune system response has been performed during the development and progression of dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. For this aim, a number of immune parameters (thymocyte and splenocyte proliferative response to T-dependent mitogens, antibody production, lymphocyte subset phenotyping, interleukin 2 receptor expression in resting and activated lymphocytes, thymus morphology and morphometry), were correlated with tumor appearance and growth at different (-7, 0, +15, +30, +60, +90, and +120 days) time intervals after intragastric administration of DMBA, in the absence or the presence of a concomitant treatment with the thymic pentapeptide thymopentin (TP5). A profound and time-dependent immunosuppression characterized the treatment with the carcinogen. Both cell-mediated and humoral immune responses showed a 50% inhibition 2 weeks after DMBA administration, with a peak after 30 days, followed by a plateau until 120 days of observation. The mechanism responsible for reduced ability of thymocytes and splenocytes to respond to both Con-A and PHA was explained by the significant inhibition of one of the key steps of T cell activation, namely the expression of IL-2 receptor in lymphocytes from DMBA-treated animals. The flow cytometric analysis of lymphocyte subpopulations revealed an important reduction in the overall populations of thymocytes and splenocytes. At the thymus gland level, a dramatic reduction of double positive CD4+CD8+ and a decrease of CD4+CD8- and CD4-CD8+ were observed, together with a marked atrophy of the thymic cortex, and impairment of the thymic microenvironment. One hundred and twenty days after DMBA administration, approximately 60 to 70% of the animals developed tumors with a mean tumor surface area of 2.88 +/- 0.86 cm2, and a number of 2.44 +/- 1.0. Treatment with TP5 (100 ng/animal, three times a week, starting a week before DMBA), produced specific effects on different immune compartments and tumoral growth, characterized by a significant reversal of immune depression with a stimulatory effect measured on lymphoproliferative assays, lymphocyte subset distribution, and IL-2 receptor expression. Moreover, thymic atrophy was almost completely prevented in TP5 treated animals. Of major interest, a significant delay in the appearance and growth of tumors was observed in TP5 treated rats. When DMBA-treated animals were followed for the entire observation period (0-120 days) and the immune responsiveness correlated according to tumor progression, stability, or regression, a positive correlation was calculated between the degree of immune system depression and the individual rate of tumor growth; in TP5-treated rats the majority of the tumors were static or regressing tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The immune system response during development and progression of carcinogen-induced rat mammary tumors: prevention of tumor growth and restoration of immune system responsiveness by thymopentin. 831 80

The interleukin 2 receptor beta chain (IL-2R beta) is preferentially expressed in natural killer (NK) cells, but is not detected in a majority of resting T and B cells. We recently established a novel monoclonal antibody (mAb) to murine IL-2R beta and examined in vivo the effect of the mAb in mice. We found that intraperitoneal injection of the anti-IL-2R beta mAb into adult mice resulted in a selective in vivo elimination of splenic NK function in various mouse strains. The reduction of NK cell function is associated with complete disappearance of NK1.1+ cells in C57BL/6 mice. Other lymphocyte subsets in the thymus and spleen were uncompromised. T cell function was not affected by the mAb treatment as judged by allogeneic cytotoxic T cell induction. The single injection of anti-IL-2R beta mAb caused a long-term elimination of splenic NK cells, lasting for at least 5 wk. We also found that NK and/or NK precursor cells become susceptible to the mAb treatment only after birth, suggesting that functional maturation of NK cells in terms of IL-2R beta expression is a later event in the course of NK cell development. The use of the anti-IL-2R beta mAb will be useful in defining the physiological role of NK cells in host defense as well as dissecting their developmental pathway in vivo.
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PMID:Selective long-term elimination of natural killer cells in vivo by an anti-interleukin 2 receptor beta chain monoclonal antibody in mice. 835 49

The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.
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PMID:Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. 850 May 19

Although tumor necrosis factor-alpha (TNF) is constitutively expressed in human and mouse thymus, the effects of TNF on thymocyte proliferation, differentiation and survival suggest that its influence in the thymus is complex. To determine if this complexity results from changes in the expression of the two TNF receptors during thymocyte differentiation, we examined the expression of the 55 kDa TNF receptor (TNF-R1) and the 75 kDa TNF receptor (TNF-R2) on postnatal human thymocytes. Both TNF-R1 and TNF-R2 mRNA were found in resting human thymocytes by reverse transcriptase-polymerase chain reaction (RT-PCR). Using mAb which specifically react with the respective TNF receptors and a highly sensitive, three-step method of immunofluorescence, cell surface TNF-R1 was detected on the vast majority of thymocytes. In contrast, detectable cell surface TNF-R2 was present on a mean of only 12.9% of thymocytes. TNF conjugated to phycoerythrin (TNF-PE) also reacted with a small population of thymocytes and was found to specifically block binding of the TNF-R2 mAb and not the TNF-R1 mAb, implicating preferential binding of TNF-PE to TNF-R2. Using dual-color immunofluorescence with TNF-PE we found that the population of cells which express TNF-R2 also express high levels of the TCR alpha, beta-CD3 complex, CD4 or CD8, and IL-2 receptor alpha chain. Thus, immature (TCRneg/low) thymocytes express TNF-R1 while mature (TCRhigh) thymocytes can also express TNF-R2. This differential expression of TNF receptors provides a mechanism for distinct effects of TNF on immature vs. mature thymocytes.
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PMID:Characterization of TNF receptors on human thymocytes. 852 4

Murine liver contains alpha beta T cells with intermediate TCR (TCRint) as well as alpha beta T cells with bright TCR. Liver TCRint cells express NK1.1 Ag (NK1+ TCRint) and IL-2 receptor beta chain, both of which are NK cell markers and are not expressed on conventional T cells. Liver NK1+ TCRint cells consist of CD4-8- double negative T cells and CD4+ T cells and have V beta 8+ T cell preponderance. They are dependent on class Ib or CD1 molecules of APC for their development. They can also develop thymus independent manner, because athymic nude mice have this population. These NK1+ TCRint cells in the livers of both euthymic and athymic mice were found to be activated by systemic administration of IL-12 and increased NK1 expression (NK1high TCRint) and cytotoxicity against various NK-sensitive and resistant tumors. Cytotoxicity assays after treatment of IL-12 stimulated hepatic MNC with respective Abs and C revealed that CD4+ NK1high TCRint cells are responsible for IL-12 induced cytotoxicity. Although NK1+ TCRint cells were normally few in the lungs, a significant proportion of NK1high TCRint cells with strong cytotoxicity was also induced in the lung by IL-12. Interestingly, adoptive transfer of IL-12 stimulated hepatic MNC into other mice, which were pre-injected with tumors, inhibits hepatic metastases of EL4 cells and pulmonary metastases of 3LL cells as similarly as IL-12 administration. Transfer experiments after treatment of IL-12 stimulated hepatic MNC with respective Ab and C revealed that depletion of either NK1+ cells, CD3+ cells or CD4+ cells but not CD8+ cells greatly impaired antimetastatic effect in both organs. Thus, CD4+ NK1high TCRint cells are a major antimetastatic population, especially, against hematogenous metastases.
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PMID:[The function and role of extrathymic T cells]. 853 54

To determine whether signaling via CD122 (interleukin-2 [IL-2]/IL-15 receptor beta-chain) plays a role in regulating the expansion and differentiation of lymphocyte precursors, we have characterized its expression and evaluated its ability to influence the activity of developing lymphoid cells. A significant fraction of Sca1+Lin- hematopoietic stem cells in day 12 fetal liver were found to be CD122+. CD122-mRNA+ and IL-2-mRNA+ cells were also localized in embryo sections within pharyngeal blood vessels adjacent to and surrounding the thymic analgen. This distribution is consistent with the migration of CD122+ progenitor cells from the liver to the developing thymus where a majority of Sca1+ intrathymic T-cell progenitors were CD122+. Analysis of CD122 expression in the day 12 fetal liver revealed that the majority of B220+ cells were CD122+. Furthermore, CD122 expression was restricted to the earliest B220+ cells (CD43+CD24-; prepro B cells; fraction A) that proliferate vigorously to IL-2 in the absence of any stromal cells, but not to IL-15. Consistent with a role for the IL-2/IL-2R pathway in lymphocyte development is the progressive loss of B cells seen in IL-2-deficient mice. Together, these observations suggest that CD122 plays a role in regulating normal lymphocyte development in vivo.
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PMID:Regulated expression and function of CD122 (interleukin-2/interleukin-15R-beta) during lymphoid development. 854 41

Glucocorticoid hormones (GCH) regulate, through the apoptotic process, the negative selection of immature T cells in the thymus. Because apoptosis seems to occur also in the maintenance of peripheral tolerance, we have investigated whether GCH may induce apoptosis in human mature lymphocytes. Peripheral blood lymphocytes (PBL) or peripheral CD4(+) and CD8(+) T cell subsets were cultured in the presence of phytohaemaglutinin (PHA) or PHA and prednisone (PDN) at 10(-3)-10(-12)M concentrations for 72, 96 and 120h. Cell cycle and membrane antigen expression were evaluated by flow cytometry and DNA degradation was detected by agarose gel electrophoresis. PDN blocks PBL growth in the G1 phase of cell cycle and inhibits both IL-2 receptor (IL-2R) expression and IL-2 secretion. Apoptosis is clearly increased by PDN in PHA-activated human PBL, and the apoptotic effect of PDN is stronger on CD8(+) than on CD4(+) T lymphocytes. All these effects are dose- and time-dependent. The addition of exogenous IL-2 did not rescue lymphocytes from PDN-increased apoptosis. These results show that PDN increases apoptosis in mature activated human peripheral blood lymphocytes, suggesting a possible role of GCH in the maintenance of immune tolerance at post-thymic level.
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PMID:Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes. 860 50

The interleukin 7 receptor (IL-7R) plays a crucial role in early B- and T-cell development. It consists of a unique a chain and a common gamma chain [IL-2 receptor gamma chain (IL-2Rgamma)]. Gene inactivation of IL-7, IL-7R, and IL-2Rgamma resulted in severe impairment of B and T lymphopoiesis in mice. In addition, IL-2Rgamma-deficient mice lack gammadelta T cells in the skin and have the impaired development of natural killer (NK) cells and intraepithelial lymphocytes. To explore the role of IL-7/IL-7R system in gammadelta T- and NK-cell development, we have generated and analyzed IL-7R-deficient mice. gammadelta T cells were absent from skin, gut, liver, and spleen in the deficient mice. In contrast, alphabeta T and B cells were detected in reduced, but certain, numbers, and NK cells developed normally. The gammadelta T-cell development in fetal and adult thymus was also completely blocked. These results clearly demonstrate that the signal from IL-7R is indispensable for gammadelta T-cell development in both thymic and extrathymic pathways. On the contrary, it is suggested that NK-cell development requires cytokine(s) other than IL-7.
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PMID:Interleukin 7 receptor-deficient mice lack gammadelta T cells. 869 64


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