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

Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly(TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly(CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the gamma chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification.
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PMID:Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency. 782 3

X-linked severe combined immunodeficiency (XSCID) is an inherited disease characterized by profoundly diminished cell-mediated and humoral immunity. XSCID was found to result from mutations in the interleukin-2 (IL-2) receptor gamma chain. Knowledge of the genetic defect has important implications for prenatal and postnatal diagnosis, carrier female identification, and the possibility of gene therapy. The fact that the phenotype and clinical manifestations in XSCID are more severe than the abnormalities found in humans or mice deficient in IL-2 led to the speculation and subsequent confirmation that the IL-2 receptor is not the only receptor to contain the gamma chain. Instead, the gamma chain is also a component of the receptors for IL-4, IL-7, IL-9, and IL-15 and is now denoted as the common cytokine receptor gamma chain, gamma c. The role of gamma c in signaling and lymphoid development and the implications of a shared receptor component are discussed.
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PMID:The molecular basis of X-linked severe combined immunodeficiency: defective cytokine receptor signaling. 871 78

Mutation of the gamma c chain common to interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors has been shown to be responsible for the X chromosome-linked severe combined immune deficiency (SCIDX1). Human SCIDX1 patients are characterized by an absence of T and natural killer cell differentiation. We report the case of a SCIDX1 patient who first had few detectable peripheral T cells, then developed, after haploidentical T-depleted bone marrow transplantation (BMT), up to 2,000/microL autologous T cells. These T cells have persisted over 8 years after BMT and were able to proliferate in the presence of mitogens and of some antigens, although to a lesser extent than control T cells. A stop mutation was identified which predicts that the major part of the cytoplasmic tail of gamma c is truncated. This mutation does not affect high-affinity IL-2 binding, but it partly decreases IL-2 endocytosis and prevents the downmodulation of the IL-2-receptor beta chain and the tyrosine phosphorylation of Jak 3 protein in response to IL-2. This report raises questions concerning the role of the gamma c chain in IL-2 receptor endocytosis and in T-cell development and differentiation.
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PMID:T-lymphocyte differentiation and proliferation in the absence of the cytoplasmic tail of the common cytokine receptor gamma c chain in a severe combined immune deficiency X1 patient. 878 27

Stat5a was identified as a prolactin-induced transcription factor but also is activated by other cytokines, including interleukin-2 (IL-2) and IL-7. We have now analyzed the immune system of Stat5a-deficient mice. Stat5a-/- splenocytes exhibited defective IL-2-induced expression of the IL-2 receptor alpha chain (IL-2R alpha), a protein that together with IL-2R beta and the common cytokine receptor gamma chain (gamma(c)) mediates high-affinity IL-2 binding. Correspondingly, Stat5a-/- splenocytes exhibited markedly decreased proliferation to IL-2, although maximal proliferation was still achieved at IL-2 concentrations high enough to titrate intermediate-affinity IL-2R beta/gamma(c) receptors. Thus, defective Stat5a expression results in diminished proliferation by an indirect mechanism, resulting from defective receptor expression. Correspondingly, we show that Stat5a is essential for maximal responsiveness to antigenic stimuli in vivo, underscoring the physiological importance of IL-2-induced IL-2R alpha expression.
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PMID:An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction. 939 Jun 92

We have characterized the T lymphocyte population of the human neonate in respect of the expression of phenotypic profiles for naive, memory and differentiated populations. We have examined the response of the neonate T cell to the superantigen Staphylococcus enterotoxin B (SEB) and compared the response to T cells from healthy adults. We found that the primary response to SEB is equivalent in neonates and adults but that the secondary response demonstrates hyporesponsiveness in the neonate that is more profound than in adults. This response was associated with increased expression of CD25; the alpha chain of the IL-2 receptor, equivalent to that seen in responding cells from adults. A modest increased expression of CD122 and CD132, the beta and gamma chains of the IL-2 receptor, was also observed. There was no increase in the IL-4 receptor (CD124). The hyporesponsive neonate T cells proliferated in response to exogenous IL-2 but the response was less than none SEB treated cells. The neonate cells did not respond to IL-4. We also examined the expression of MHC class II molecules on SEB stimulated cells and found that both neonate and adult T cells upregulate MHC class II to a similar degree. The difference in the hyporesponsive cells appears to result in part from a lower production of IL-2 and in part from a lower ability of cord cells to respond to IL-2. Since the stimulated cord cells expressed IL-2 receptor at the same levels as similarly treated adult cells; there may be differences in down stream signaling pathways.
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PMID:Analysis of the cord blood T lymphocyte response to superantigen. 1002 80

The Trypanosoma cruzi membrane glycoprotein AGC10 has been shown to alter some human macrophage functions (De Diego, J. L. et al., J. Immunol. 1997. 159: 4983-4989). We show here that, in the presence of AGC10, [3H]thymidine incorporation by normal human lymphocytes stimulated with anti-CD3 or phytohemagglutinin (PHA) is severely curtailed. This effect was found to involve down-regulation of the expression of both CD25 (IL-2R alpha) and CD122 (IL-2R beta) on the lymphocyte membrane and a marked decrease in the level of up-regulation of the expression of surface CD132 (IL-2R gamma or gamma(c)). These alterations occurred in fairly large proportions of CD4+ and CD8+ lymphocytes. AGC10 also inhibited proliferation and expression of IL-2 receptor chains by activated T lymphocytes virtually depleted of monocytes/macrophages, indicating that these effects do not necessarily require prior modification of monocyte/macrophage function by AGC10. Human lymphocytes stimulated with anti-CD3 or PHA also displayed a markedly decreased capacity to secrete IL-2 and IFN-gamma, suggesting that AGC10 affected at least Th1 cell functions. Cell viability in cultures containing or lacking AGC10 was comparable over a 72-h period, and neither CD25 expression by, nor the viability of, PHA-stimulated Jurkat cells was altered by AGC10, ruling out that the effects of AGC10 are due to cell killing. These results highlight down-regulatory effects on activated T lymphocytes exerted by a membrane molecule from a parasite causing a disease whose acute phase is accompanied by immunosuppression.
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PMID:Inhibitory effects of the Trypanosoma cruzi membrane glycoprotein AGC10 on the expression of IL-2 receptor chains and secretion of cytokines by subpopulations of activated human T lymphocytes. 1035 23

Lethal shock can be associated with excessive secretion of cytokines such as tumor necrosis factor (TNF) and gamma interferon (IFN-gamma). IFN-gamma mediates macrophage activation and appears to be controlled by interleukin (IL)-12 and IL-18. To investigate the role of IL-18 in vivo, we generated IL-18-deficient mice by gene targeting. IL-18(-/-) mice showed decreased sensitivity towards lipopolysaccharide (LPS)-induced shock. LPS-induced IFN-gamma production was abrogated, yet induction of IL-12 and TNF was not affected. Both wild-type and IL-18-deficient mice succumbed to LPS-induced lethal shock after sensitization with D-galactosamine. However, in marked contrast to LPS, the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) induced comparable serum levels of IFN-gamma in IL-18(+/+) and IL-18(-/-) mice, accompanied by an upregulation of cell surface markers CD14, CD122 (IL-2Rbeta), and CD132 (IL-2Rgamma) on peritoneal macrophages. Moreover, SEB injection rendered IL-18-deficient mice sensitive for subsequent challenge with LPS. The degree of sensitization was comparable to that in wild-type controls with respect to lethality. However, LPS-induced TNF levels in serum were significantly reduced in SEB-sensitized IL-18-deficient mice. These results imply that IL-18 plays an important role in induction of IFN-gamma and lethality in response to LPS.
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PMID:Role of interleukin-18 (IL-18) during lethal shock: decreased lipopolysaccharide sensitivity but normal superantigen reaction in IL-18-deficient mice. 1081 4

Owing to the contrasting observations in the field of interleukin(IL)-2 receptor research, the expression of IL-2 receptor chains was analysed on resting and anti-CD3 antibody (OKT3) activated CD4 and CD8 T cells by flow cytometry. Prior to the stimulation, 49% of CD4+ cells expressed IL-2Ralpha (CD25), whereas the expression of IL-2Rbeta (CD122) was very low (8%). The reverse was true for CD8 cells: 48% of them were positive for CD122, but only a fraction (10%) expressed CD25. Practically all lymphocytes expressed IL-2Rgamma (CD132). Interestingly, the unbalanced expression of IL-2Ralpha and -beta continued throughout the stimulation period of 2 days. In addition, the expression of CD45 isoforms in combination with the IL-2R chains and CD71 was followed during the activation of CD4+ T cells. Although CD45RA+/RO- CD4 cells were effectively activated, they retained their naive phenotype up to 2 days of stimulation. On the other hand, CD45RA+low/RO+low (Ddull) CD4+ cells shifted to the memory phenotype rapidly after being activated. However, by day 6 of stimulation the shift of both naive and Ddull cells to memory ones was obvious. The role of the IL-2 receptor in the activation of CD4 subpopulations is discussed.
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PMID:T-lymphocyte subpopulations do not express identical combinations of interleukin-2 receptor chains in the early phase of their activation and proliferation. 1093 79

We have identified a type I cytokine receptor, which we have termed novel interleukin receptor (NILR), that is most related to the IL-2 receptor beta chain (IL-2Rbeta) and physically adjacent to the IL-4 receptor alpha chain gene on chromosome 16. NILR mRNA is most highly expressed in thymus and spleen, and is induced by phytohemagglutinin in human peripheral blood mononuclear cells. NILR protein was detected on human T cell lymphotropic virus type I-transformed T cell lines, Raji B cells, and YT natural killer-like cells. Artificial homodimerization of the NILR cytoplasmic domain confers proliferation to Ba/F3 murine pro-B cells but not to 32D myeloid progenitor cells or CTLL-2 murine helper T cells. In these latter cells, heterodimerization of IL-2Rbeta and the common cytokine receptor gamma chain (gamma(c)) cytoplasmic domains allows potent proliferation, whereas such heterodimerization of NILR with gamma(c) does not. This finding suggests that NILR has signaling potential but that a full understanding of its signaling partner(s) is not yet clear. Like IL-2Rbeta, NILR associates with Jak1 and mediates Stat5 activation.
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PMID:Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. 1101 59

The effects of purified AGC10, a Trypanosoma cruzi membrane glycoprotein, on normal human B lymphocytes were studied in this work. In the presence of AGC10, [3H]-thymidine uptake by human peripheral blood mononuclear cells stimulated with the B cell-specific mitogen SACI (killed Staphylococcus aureus Cowan I) was markedly decreased. This alteration was accompanied by others such as decreased expression of the CD122 and CD132 chains of the IL-2R complex. These inhibitory effects appeared to be somewhat selective, as expression of CD25, another IL-2R chain, was not affected by AGC10 and no significant modification occurred in the expression of the B-cell-specific marker CD19 or CD21. In contrast, AGC10 did reduce the levels of expression of CD86 and CD80, molecules known to play critical roles in B cell interactions with T lymphocytes. Fairly large subpopulations of, but not all, B lymphocytes had their expression of CD122(+), CD132(+), CD86(+) and CD80(+) reduced to undetectable levels in the presence of AGC10. However, the SACI-activated B cells that remained capable of expressing these molecules in the presence of AGC10 did so at normal levels. This was denoted by comparable mean fluorescence intensity values representing the expression of CD122, CD132, CD86 or CD80 molecules on the surface of SACI-stimulated CD19(+) cells cultured without or with AGC10. These results indicated that AGC10, derived from an organism that causes immunosuppression in infected hosts, down-regulates B cell activities and suggested that the relevant mechanism could involve the molecular alterations described above.
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PMID:Down-regulation of human B lymphocyte activities by a Trypanosoma cruzi membrane glycoprotein. 1122 53


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