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

Peripheral blood (PBL) and synovial fluid lymphocytes (SFL) from 18 patients with definite rheumatoid arthritis (RA) and from one patient with Reiter's disease (RD) were examined for their capacity to absorb quantitatively interleukin-2 (IL-2) from a standardized, lectin-free IL-2 source. For comparison normal ConA blasts and PBL from various inflammatory and noninflammatory diseases as well as from healthy control persons were studied. IL-2 activity was quantitated by measuring 3H-thymidine-2-deoxyriboside uptake in the IL-2 dependent murine T cell line CTL6. ConA blasts exhibited a high IL-2 absorption capacity and served as a positive control for calibrating the absorption assay. In a population of normal PBL at least 5-10% of ConA blasts were required to detect IL-2 absorption. Significant absorption was assumed if more than 50% of IL-2 activity was removed from 200 microliters of a lectin-free IL-2 standard following incubation with 5 X 10(6) lymphoid cells for 2 h at 4 degrees C; this criterion was fulfilled with 8 out of 20 SFL and 4 out of 14 PBL preparations from RA patients. As a rule SFL absorbed more IL-2 than PBL. Control PBL did not absorb significant quantities of IL-2. PBL from the RD patient apparently produced an IL-2 inhibitor during incubation with the IL-2 standard. IL-2 absorption by ConA blasts and SFL was fully inhibited by preincubation of the absorbing cells with monoclonal anti-TAC antibody, a reagent known to react with the human IL-2 receptor. The results are discussed in view of current concepts of antigen/mitogen induced T cell activation.
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PMID:Quantitative absorption of interleukin-2 by peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. 392 39

The identification of T cells in the brain using monoclonal antibodies has suggested a role for T cells in the pathogenesis of multiple sclerosis (MS). In the present study the monoclonal antibody anti-Tac, shown to react with interleukin-2 (IL-2) receptors expressed on activated T cells, was used to determine levels of recently activated T cells in blood, cerebrospinal fluid (CSF) and brain sections from MS patients at different stages of disease. The CSF of MS patients contained much higher numbers of IL-2 receptor positive lymphocytes (up to 67%) than blood cells from the same patients, or the CSF of patients with non-inflammatory neurological diseases. In histological sections of the brain of MS patients with active disease, perivascular lymphocytes expressing IL-2 receptors were detected, as were lymphocytes containing IL-2. In contrast, these were absent in brain sections from patients with chronic MS, secondary demyelination or from normal controls. These observations in CSF and brain suggest that in multiple sclerosis, T-cell activation is occurring within the CNS and not in peripheral lymphoid tissue.
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PMID:The distribution of interleukin-2 receptor bearing lymphocytes in multiple sclerosis: evidence for a key role of activated lymphocytes. 393 Jan 9

We have established the DU.528 cell line from the pretreatment leukemia cells of a patient who underwent a T lymphoblastic-to-promyelocytic phenotype conversion during treatment with the adenosine deaminase inhibitor, deoxycoformycin. The cell line and clones obtained from it by limiting dilution have the same karyotype previously found in the patient's pretreatment T lymphoblasts and post-deoxycoformycin treatment promyelocytes. DU.528 cells in continuous culture for greater than 2 yr display a predominant undifferentiated T lymphoblastoid phenotype. These cells spontaneously generate progeny of at least three lineages, T lymphoid, granulocytic/monocytic, and erythroid. The surface marker most consistently expressed by DU.528 cells in the undifferentiated state is the 3A1 antigen, which has been found on prothymocytes in the embryonic thymus. Some undifferentiated DU.528 cells also expressed the IL-2 receptor, but no other T cell differentiation antigens. Exposure of DU.528 cells to a variety of agents induced myeloid maturation; adenosine and deoxyadenosine, in the presence of deoxycoformycin, induced expression of myeloid differentiation antigens. Our results suggest that DU.528 is a lymphohematopoietic stem cell line and support the hypothesis that differentiation of pluripotent stem cells may be altered by genetic deficiency of adenosine deaminase. DU.528 cells may provide a useful model for examining factors that regulate stem cell proliferation and differentiation.
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PMID:Establishment of the DU.528 human lymphohemopoietic stem cell line. 405 59

Interleukin-2 (IL-2) is a lymphokine synthesized by some T cells following activation. Resting T cells do not express IL-2 receptors but receptors are rapidly expressed on T cells following the interaction of antigens, mitogens, or monoclonal antibodies with the antigen specific T-cell receptor complex. Using anti-Tac a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified. The receptor is a 33 kdalton peptide that is post-translationally glycosylated to a 55 kdalton mature form. Mature receptors contain both N-linked and O-linked sugars and are both sulfated and phosphorylated. Using an oligonucleotide probe, based on the N-terminal amino acid sequence, cDNAs encoding this receptor have been cloned, sequenced and expressed. The addition of anti-Tac to in vitro culture systems blocks the IL-2 induced DNA synthesis of IL-2 dependent T-cell lines and inhibits soluble auto- and alloantigen induced T-cell proliferation. Furthermore, it prevents the generation of cytotoxic and suppressor effector T cells. The anti-receptor antibody also inhibits lectin stimulated immunoglobulin synthesis and the sequential expression of late appearing activation antigens on T cells. Normal resting T cells and most leukemic T-cell populations do not express IL-2 receptors however the leukemic cells of all patients with human T-cell leukemia/lymphoma virus (HTLV-I) associated, adult T-cell leukemia (ATL) examined expressed the Tac antigen. In HTLV-I infected cells the 42 kdalton long open reading frame (LOR) protein encoded in part, by the pX region of HTLV-I may act as a transacting transcriptional activator that induces transcription of the IL-2 receptor gene thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2 receptor expression. The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T cells. Patients with the Tac positive ATL are being treated with an anti-Tac monoclonal antibody directed towards this growth factor receptor.
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PMID:Interleukin-2 receptor expression in retrovirus associated adult T-cell leukemia. 610 Jun 44

We have established non-lymphoid cell lines HeLa, Ltk and NIH3T3 expressing the human interleukin-2 (IL-2) receptor by transfection of human IL-2 receptor complementary DNA. While IL-2 receptors on T cells are classified into the high and low affinity species, the receptors expressed on the cDNA-transfected non-lymphoid cells belong to the low affinity species. These IL-2 receptors could not transmit the growth signal although they were similar in size to those expressed on T cells. Phorbol ester-induced phosphorylation of the IL-2 receptors on HeLa cells did not affect the affinity of the receptor. We have also constructed a cDNA encoding a mutant IL-2 receptor that replaced the major phosphorylation site, the serine residue at position 247 with the glycine residue. This mutant IL-2 receptor expressed on non-lymphoid cells also had the low affinity for IL-2. The results indicate that the high and low affinity states of the IL-2 receptor are not solely determined by phosphorylation of the receptor. The IL-2 receptors expressed on these non-lymphoid cells were internalized four to eight times more slowly than those on T cells. Possible defects of the IL-2 receptors expressed on non-lymphoid cells are discussed.
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PMID:Properties of human interleukin-2 receptors expressed on non-lymphoid cells by cDNA transfection. 644 99

Reconstitution with mouse interleukin-2 (IL-2) receptor subunits demonstrated that the mouse IL-2 receptor complex was different from the human complex in the alpha chain requirement for the functional mouse receptor complex. The heterotrimeric complex of the mouse exogenous alpha and beta chains and the endogenous gamma chain on mouse lymphoid BW5147 cells showed the ability to bind IL-2 with high affinity, resulting in IL-2-induced tyrosine phosphorylation of a cytosolic tyrosine kinase, JAK3, which is involved in IL-2-dependent signals. Exogenous introduction of the beta chain with the endogenous gamma chain, however, could neither confer appreciable IL-2 binding nor IL-2-induced signal transduction on BW5147 cells, unlike the human beta gamma heterodimer. Mouse spleen CD8+ cells, not having the alpha chain initially, showed IL-2-dependent cell proliferation only when expression of the alpha chain was induced. Collectively, these results illustrate that the functional mouse IL-2 receptor complex necessarily includes the alpha chain, and that the regulation of CD8+ T cell growth during immune reaction depends upon alpha chain expression.
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PMID:Differences in the interleukin-2 (IL-2) receptor system in human and mouse: alpha chain is required for formation of the functional mouse IL-2 receptor. 748 34

Dendritic epidermal T cells (DETC) are skin-specific members of the epithelial gamma delta T-cell family in mice. We have reported previously that the growth of DETC is promoted by interleukin (IL)-2 in an autocrine fashion, or by IL-7, which is secreted by neighboring keratinocytes. Here we report that DETC growth is promoted by IL-15, a newly discovered T-cell growth factor that is produced in lymphoid as well as nonlymphoid tissues. Recombinant IL-15 promoted the growth of the 7-17 DETC line in a time- and dose-dependent fashion. Using monoclonal antibodies against alpha-, beta-, or gamma c-chains of the IL-2 receptor complex, we observed that the combination of anti-beta chain and anti-gamma c chain antibodies blocked IL-15 responsiveness completely, whereas anti-alpha chain had no effect. These results indicate that this gamma delta T-cell line uses the beta/gamma c heterodimer for proliferative responses to IL-15. Antibodies against IL-2 or IL-7 did not block IL-15-driven proliferation of 7-17 DETC, indicating that IL-15 promotes their growth in an IL-2- and IL-7-independent manner. Both the surface expression of beta/gamma c heterodimers and the IL-15 responsiveness of 7-17 DETC were highest 1 to 8 days after concanavalin A stimulation, and both declined substantially 21 days after stimulation, illustrating regulation by the state of cell activation. Working with epidermal cells that were freshly procured from CBA mice, we noted that IL-15 promoted conavalin-A-triggered growth of Thy-1+ cells (i.e., DETC), but not of the Thy-1- cells. The gamma c-chain was not expressed by freshly procured DETC, becoming detectable within 48 h after concanavalin A stimulation. We propose that IL-15 facilitates the growth of epithelial gamma delta T cells by a beta/gamma c receptor-dependent mechanism.
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PMID:Interleukin (IL)-15 promotes the growth of murine epidermal gamma delta T cells by a mechanism involving the beta- and gamma c-chains of the IL-2 receptor. 749 Apr 80

The cellular and molecular regulation of IL-4 mRNA expression in human tonsillar T lymphocytes was examined to define the mechanisms responsible for biphasic IL-4 mRNA expression in this lymphoid organ. Tonsillar T cells expressed IL-4 mRNA in a biphasic manner with peaks at 8 and 24 h after PHA stimulation. De novo protein synthesis was not required for IL-4 mRNA expression because cycloheximide treatment of tonsillar MNC did not ablate the response. Nuclear runoff assays demonstrated transcription of the IL-4 gene at 8 and 24 h, which was not affected by addition of actinomycin D. Separation of T cells into naive (CD45RAhi/CD29lo) and primed (CD45RAlo/CD29hi) subpopulations revealed that although naive and primed T cells expressed IL-4 mRNA at 8 h, the 24-h peak of IL-4 mRNA expression was solely due to primed (CD45RAlo/CD29hi) Th cells. This effect was tissue specific and IL specific in that 1) primed peripheral blood T cells had only one peak of IL-4 mRNA expression at 8 h and 2) in primed tonsillar T cells, mRNA expression of IL-2, IL-6 and IL-2 receptor and c-myc was not delayed. Thus, IL-4 mRNA expression in the tonsil differs depending on the surface expression of different isoforms of the leukocyte common Ag. The tissue- and stimulus-specific regulation of IL-4 mRNA in different lymphoid tissues may play an important role in regional immunoregulation.
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PMID:Tissue-specific regulation of IL-4 mRNA expression in human tonsil. 750 59

Janus tyrosine kinase (JAK) has recently been linked to signal transduction by cytokine receptors of the hematopoietin family. We have recently described a 116-kDa tyrosine kinase (p116) present in interleukin-2 (IL-2) receptor complexes in human YT cells that showed functional characteristics of a JAK kinase. These included receptor association, rapid and transient tyrosine phosphorylation kinetics in response to ligand, and in vitro autophosphorylating tyrosine kinase activity (Kirken, R. A., Rui, H., Evans, G. A., and Farrar, W. L. (1993) J. Biol. Chem. 268, 22765-22770). Here we extend these observations by demonstrating structural homologies between IL-2-modulated p116 and prolactin-modulated JAK2 in the rat T cell line Nb2. These include similar net charge as determined by nonequilibrium pH gradient electrofocusing and related primary structure based upon phosphopeptide mapping of V8 protease-digested hyperphosphorylated proteins. This putative JAK kinase underwent marked tyrosine phosphorylation in response to IL-2, IL-4, and IL-7, lymphoid growth factors that use the common IL-2 receptor gamma-chain, but not in response to prolactin. Furthermore, polyclonal antisera to JAK1, JAK2, or tyrosine kinase 2 did not recognize either rat or human p116. However, we identified the IL-2-modulated p116 as the recently cloned novel leukocyte Janus kinase, L-JAK, using an antiserum to a peptide corresponding to the COOH terminus of human L-JAK.
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PMID:Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase. 751 51

A small subpopulation of CD4+ T cells found in peripheral blood coexpresses the CD57+ marker normally found on, e.g., NK cells. It is known that this population occurs in a higher frequency in certain diseases. The same antigen has also been shown to be expressed on CD4+ T cells derived from germinal centers. The localization of this cell population to specialized lymphoid structures suggests that it may play a role in the evolution of the antibody response following antigenic stimulation in vivo. We have examined the ability of peripheral blood helper T cells coexpressing CD57 to participate in B cell activation/differentiation and evaluated their responses to polyclonal stimulation. The CD4+CD57+ T cells do not express mRNA for a number of different cytokines or for the CD40 ligand after activation in vitro. Furthermore these cells do not induce differentiation of B cells into immunoglobulin-producing cells. Consequently, despite their CD4 phenotype and their ability to be activated, to express the IL-2 receptor, and to enter into the cell cycle, they do not act as T helper cells under conditions where CD4+/CD57- cells normally do so. The findings suggest that this peripheral blood helper T cell population is functionally different from regular CD4+ T cells. The basis for the lack of proper costimulatory signals for immunoglobulin production might be related to the low expression of CD28.
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PMID:CD4+CD57+ T cells derived from peripheral blood do not support immunoglobulin production by B cells. 754 27


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