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)

Study of the network of cytokines has helped identify cell growth factors in multiple myeloma. Plasma cells themselves may produce autocrine interleukin 6 (IL-6) while IL-6 production by bone marrow stromal cells may operate a paracrine mechanism. Involvement of IL-6 in multiple myeloma is indicated by its ability to induce the differentiation of myeloma plasmablasts into mature malignant plasma cells. Differential diagnosis between multiple myeloma and monoclonal gammopathies of undetermined significance (MGUS) is generally based on clinical and laboratory parameters. Nevertheless, evaluation of the serum level of IL-6, C reactive protein, soluble IL-6 receptor, soluble IL-2 receptor together with the activity exerted by IL-3 and IL-4 on some cellular subsets constitutes an additional element in the differential diagnosis of border-line cases. Serum levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R) and the expression of membrane-bound IL-2 receptors, both on bone marrow plasma cells and on peripheral blood mononuclear cells are correlated with disease activity and disease stage. In addition, IL-6 and sIL-6R serum levels correlate with the duration of survival, as high values at the time of diagnosis correlate with short duration of survival.
Cytokine 2001 Nov 07
PMID:Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data. 1174 46

Interleukin-2 (IL-2) plays a major role in the proliferation of cell populations during an immune reaction. The beta(c) and gamma(c) subunits of the IL-2 receptor (IL-2R) are sufficient and necessary for signal transduction. Despite lacking known catalytic domains, receptor engagement leads to the activation of a diverse array protein tyrosine kinases (PTKs). In resting or anergised T cells, Jak3 is not activated. Signals arising from the PROX domain of the gamma(c) subunit activate p56(lck) (lck) leading to the induction of anti-apoptotic mechanisms. When Jak3 is activated, in primed T cells, other PTKs predominantly mediate the induction of anti-apoptotic mechanisms and drive cellular proliferation. This review intends to suggest a role for these differences within the context of the immune system.
Cytokine Growth Factor Rev 2002 Feb
PMID:Alternate signalling pathways from the interleukin-2 receptor. 1175 Aug 78

In this study, we assessed the expression of activation markers on gammadelta T cells in central nervous system (CNS) lesions of SJL mice adoptively sensitized to develop experimental autoimmune encephalomyelitis (EAE) using myelin basic protein-reactive T cells. Although disease expression is known to be dependent upon T cells that express the alphabeta T cell receptor (TCR), a role for gammadelta T cells has been implicated in some studies but not in others. Using three-color flow cytometric analysis of both total and gammadelta T cells in spleen and CNS, the data showed that expression of CD69 (early activation marker), CD62L (lymphocyte homing receptor), CD25 (IL-2Ralpha), CD122 (IL-2Rbeta) and CD95/CD95L (Fas/FasL), fluctuated on gammadelta T cells in EAE lesions in a disease-related fashion. Furthermore, the pattern of expression for these markers on gammadelta T cells was distinct from that found on the total lymphocyte population. Cytokine analysis of gammadelta T cells in the CNS demonstrated a bias towards a Th1-like cytokine profile. From these data, we conclude that gammadelta T cells in EAE lesions display an activated phenotype and form a dynamic component of the total lymphocyte population in the CNS, supporting a contributory role for these cells.
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PMID:gammadelta T cells express activation markers in the central nervous system of mice with chronic-relapsing experimental autoimmune encephalomyelitis. 1177 50

Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.
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PMID:Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients. 1182 83

Interleukin (IL) 2 receptor subunit alpha (IL-2Ralpha) increases the affinity of the IL-2 receptor complex while hetero-association of IL-2Rbeta and gamma(c) chains initiates a proliferative signal. We show here that IL-2Ralpha is necessary for receptor clustering required for augmentation of IL-2 signalling. Cells expressing chimeras incorporating the extracellular domain of IL-2Ralpha demonstrated IL-2 independent homo-association of the IL-2Ralpha chimera. Singly or co-transfected IL-2Rbeta and gamma(c) chimeras showed no spontaneous or IL-2-inducible oligomerization. Co-transfection of IL-2Ralpha and IL-2Rbeta (+/- gamma(c)) chimeras diminished spontaneous IL-2Ralpha chimera oligomerization and permitted IL-2-inducible hetero-oligomerization of receptor components. Homo-association of IL-2Ralpha was also demonstrated by fluorescence resonance energy transfer (FRET). The spontaneous homo-oligomerization property of IL-2Ralpha required the membrane proximal region of the receptor (exon 6) by deletion analysis; the IL-2 inducible oligomerization property of IL-2Ralpha required the second "sushi" domain (exon 4). This work provides insight into the mechanics of this complex receptor system and to other receptor complexes in the immune system that send signals by clustering receptor subunits.
Cytokine 2002 Jan 21
PMID:Oligomerization of IL-2Ralpha. 1188 75

Cytokines are secreted proteins that act as local immunological mediators. Increased seminal cytokine concentrations are associated with fertility problems. The purpose of the present study was to investigate the presence of IL-2alpha, and IL-2beta receptors on fresh and isolated sperm by flow cytometry and transmission electron microscopy. Twenty sperm samples from oligospermic men were incubated with CD25, a mouse monoclonal antibody specific for IL-2alpha-chain receptor, and CD122, a mouse monoclonal antibody specific for IL-2beta-chain receptor. The strong initial fluorescence intensity and, subsequently, a labeling index yielded by CD25 and CD122 decreased in sperm centrifuged on a Percoll gradient (p < .05). The expression of CD25 and CD122 correlated negatively with fresh sperm concentration, but in sperm centrifuged on a Percoll gradient there was no correlation. Labeling with CD25 and CD122 antibody was evident on the head and the middle piece in fresh sperm, while in sperm centrifuged on a Percoll gradient a weak labeling was observed only on the principal piece. The authors have identified and localized cytokine receptors on human sperm for the first time. Cytokine receptors may be involved in the regulation of pathophysiological events in sperm cell functions and male infertility. The exact pathway involved in modulation of these receptors requires further investigation. These results contribute to the understanding of cytokine-sperm relationships.
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PMID:Expression of IL-2alpha and IL-2beta receptors on the membrane surface of human sperm. 1223 Aug 26

The interleukin-2 receptor alpha (IL-2Ralpha) forms, together with IL-2Rbeta and gammac chains, a high affinity IL-2 receptor that is important for IL-2 responsiveness and normal T cell function. Expression of the IL-2Ralpha gene by T cells is regulated mainly at the transcription level which is transiently activated by antigen and upregulated and then prolonged by stimulation with IL-2. The effect of IL-2 on the IL-2Ralpha gene depends on the activation of the transcription factor Stat5, which acts on an IL-2- responsive enhancer that consists of two Stat5 and an Elf1 binding site. To identify the functional domains of the IL-2 receptor required for the stimulation of IL-2Ralpha gene expression, we introduced, into the CTL44 T cell line, receptor chimeras between the extracellular domain of the IL-9 receptor and the cytoplasmic region of IL-2Rbeta. Analyzing the effect of mutations in the intracellular IL-2Rbeta segment, we found that a minimal receptor containing the Jak boxes and one intact Stat5 docking site (i.e. tyrosine 392 or 510) can, as expected, mediate Stat5 activation, but is unable to stimulate IL-2Ralpha expression. However, when this minimal receptor includes the region between the two tyrosines, its capacity to mediate IL-2Ralpha cell surface expression is restored. These data suggest that the segment between the two Stat5 docking sites of the IL-2Rbeta chain mediates signaling events that, together with Stat5 activation, are essential for the stimulation of IL-2Ralpha gene transcription.
Eur Cytokine Netw
PMID:Induction of interleukin-2 receptor alpha (IL-2Ralpha) expression by interleukin-2: important role of the interleukin-2 receptor beta chain region between the two Stat5 docking sites. 1223 77

Interleukin (IL-) 2 and IL-15 share the IL-2 receptor betagamma c subunits (IL-2Rbetagamma c) but have specific, unique alpha receptor subunits. We studied species specificity of human (hu), simian (si), and mouse (mu) IL-15 and found that hu and si IL-15 behaved similarly in all systems investigated. Hu and mu IL-15 bound hu or mu IL-15Ralpha with equal high affinity in the presence or absence of IL-2Rbetagamma c and exhibited similar proliferative activities on cells containing all three subunits. However, quantitative differences were noted in the specific activity of hu and mu IL-15 in both in vitro and in vivo systems utilizing IL-2Rbetagamma c in the absence of IL-15Ralpha. These data show that hu IL-15 may be used in mouse model systems, however care must be taken when comparing the efficacy and toxicity of cytokines across species.
Cytokine 2002 Nov 07
PMID:Interleukin-15 interactions with interleukin-15 receptor complexes: characterization and species specificity. 1245 70

Both innate and adaptive immune systems are thought to participate in the pathogenesis of rheumatoid arthritis in adults and children. The experiments reported here were undertaken to examine how immune complexes, potent stimulators of inflammation, may regulate cells of the adaptive immune system. Human T cells were prepared from peripheral blood by negative selection and incubated with bovine serum albumin (BSA)-anti-BSA immune complexes that were formed in the presence or absence of human C1q. C1q-bearing immune complexes, but not unopsonized complexes, elicited both TNF-alpha and IFN-gamma secretion from human T cells. Secretion of both cytokines was time- and dose-dependent. Cross-linking C1q on the cell surface of T cells produced the same results. Cytokine secretion was not inhibited by blocking the C3b receptor (CR1, CD35) on T cells prior to incubation with immune complexes. Reverse transcriptase polymerase chain reaction (RT-PCR) of immune complex-stimulated cells revealed accumulation of both TNF-alpha and IFN-gamma mRNA within 2 h post-stimulation. IL-2 was not detected in cell culture supernatants, but IL-2 receptor alpha chain (CD25) was detected in low density on a small proportion of T cells activated by C1q-bearing immune complexes. Secretion of both cytokines was inhibited partially, but not completely, by IL-10. These experiments show that immune complexes, potent inflammatory mediators, may activate T cells through a novel mechanism. These findings have implications for chronic inflammatory diseases in humans.
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PMID:T cell activation by soluble C1q-bearing immune complexes: implications for the pathogenesis of rheumatoid arthritis. 1251 87

The role of CD2 signaling in cytotoxic T lymphocyte (CTL) development was examined by stimulating mouse T cells with anti-CD3 monoclonal antibody (mAb) in the absence or presence of anti-CD2 mAb or anti-CD48 mAb or both. Induction of nonspecific CTL and interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) synthesis were impaired in the absence of CD2-CD48 interactions. Anti-CD2 mAb also inhibited activation-induced expression of the high-affinity IL-2 receptor (IL-2R). In contrast, IFN-gamma receptor (IFNGR) expression was increased in the presence of anti-CD2 mAb. Reduced cytotoxicity by CTL induced in the absence of CD2-CD48 interactions was associated with a diminished ability of CTL to conjugate with target cells and reduced expression of granzyme B and perforin. Anti-CD2 mAb did not affect expression of Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by anti-CD3-activated T cells. Cytotoxic effector function and granzyme B and perforin expression were rescued when exogenous IL-2 and IFN-gamma were added in combination with anti-CD2 mAb to anti-CD3-activated T cells at initiation of culture. We conclude that CD2-CD48 interactions during T cell activation are critical for the synthesis of sufficient IL-2 and IFN-gamma to drive CD8(+) T cells to differentiate into functional cytotoxic effector cells.
J Interferon Cytokine Res 2003 Feb
PMID:CD2-CD48 interactions promote cytotoxic T lymphocyte induction and function: anti-CD2 and anti-CD48 antibodies impair cytokine synthesis, proliferation, target recognition/adhesion, and cytotoxicity. 1274 72


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