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)

We studied the effect of protein-bound polysaccharide PSK on the activation of the human natural killer cell line NKL. We observed an increased natural killer cytotoxic activity against different tumor cells (K562, Daudi, and U937) when a standard 2- to 3-h 51chromium release assay was performed. The results parallel those obtained after treatment of the NKL cell line with interleukin-2. The highest cytotoxic activity was reached at a concentration of 100 microg/ml of PSK. This natural killer activation was inhibited when the PSK dose was 1,000 microg/ml. None of the cell surface markers that were analyzed by fluorescence-activated cell sorting showed variations after PSK or interleukin-2 treatment of NKL cells. These markers included CD2, CD11b, CD11c, CD18, CD16, CD54, CD56, CD98, CD25, CD122, HLA class I, HLA class II, CD94, ILT2, p58.1, p70, and NKp46. One of these markers (NKp46) is a major triggering receptor reported to be involved in the natural cytotoxicity of fresh or cultured human natural killer cells. In our study, another triggering receptor must be implicated in PSK-induced natural killer lysis. Our data suggest that PSK is an important biological response modifier of natural killer cells in vitro and may prove to be useful for the study of human natural killer cell biology.
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PMID:Protein-bound polysaccharide (PSK) induces cytotoxic activity in the NKL human natural killer cell line. 1078 73

Profound cellular immunodeficiency occurs as the result of mutations in proteins involved in both the differentiation and function of mature lymphoid cells. We describe here a novel human immune aberration arising from a truncation mutation of the IL-2 receptor alpha chain (CD25), a subunit of the tripartite high-affinity receptor for IL-2. Decreased numbers of peripheral T cells displaying abnormal proliferation but normal B-cell development characterize this immunodeficiency. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. Although displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1. Furthermore, they fail to down-regulate levels of bcl-2 and, subsequently, apoptosis in the thymus is markedly reduced, resulting in expansion of autoreactive clones in multiple tissues.
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PMID:Human IL-2 receptor alpha chain deficiency. 1087 93

Intestinal intraepithelial lymphocytes (i-IEL) represent one of the largest, non-organized lymphoid population in the body. They are located outside the epithelial basement membrane among the mucosal epithelial cells. We, and previously other groups, have reported the presence of a CD7+CD3-IEL subset in the epithelium of human small intestine. This subset is drastically reduced in coeliac disease (CD) patients. In the present work we accomplish a better phenotypic characterization of this CD3-IEL subset and demonstrate the expression of typical natural killer (NK) cell markers. Most, if not all, CD3-CD7+ cells express NKPR1 (CD161)[98% +/- 2] and CD122[92% +/- 6]. In addition, a variable percentage express CD2[55% +/- 16], CD94[24% +/- 18], CD56[44% +/- 21] and CD16[12% +/- 4], however, no CD57 expression was observed. Moreover, these cells contain perforin granules[75% +/- 5], supporting a potential cytolytic ability. Regarding adhesion molecules, CD18 and CD44 expression is absent, which is consistent with a limited capacity of migration. Altogether, these data suggest the presence of intraepithelial NK cells in human intestinal epithelium, a compartment where cytotoxic effectors have not been clearly defined.
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PMID:Intestinal intraepithelial lymphocytes contain a CD3- CD7+ subset expressing natural killer markers and a singular pattern of adhesion molecules. 1088 77

We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)-2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity against murine melanoma induced by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35) and TRP-2(181-188). This combination therapy led to the complete rejection of a lethal challenge with B78D14 murine melanoma cells in six of eight mice and a marked suppression of s.c. tumor growth in the two remaining animals. The tumor-protective immunity was mediated by MHC class I antigen- restricted CD8(+) T cells together with CD4(+) T cell help, which was required only for tumor cell killing in the effector phase of the immune response. A single oral vaccination with the DNA vaccine, which was carried by attenuated Salmonella typhimurium, was equally as effective as three such vaccinations applied at 2-week intervals. The immunological mechanisms involved in this antitumor effect were suggested by a decisively increased secretion of tumor necrosis factor alpha TNFTnTNa and IFN-gamma from CD4(+) and CD8(+) T cells and a markedly up-regulated expression on CD8(+) T cells of high-affinity IL-2 receptor alpha chain (CD25), costimulatory molecule CD28, and adhesion molecule lymphocyte function-associated antigen-2 (LFA-2/CD2). Additionally, the combination therapy induced increased expression of costimulatory molecules B7.1 and CD48 on murine antigen-presenting cells. Taken together, our results suggest that IL-2 targeted to the tumor microenvironment by a specific antibody-IL-2 fusion protein is a potent enhancer of tumor-protective immunity induced by an oral DNA vaccine that may ultimately enhance the chances of success in its clinical application.
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PMID:Targeted interleukin 2 therapy enhances protective immunity induced by an autologous oral DNA vaccine against murine melanoma. 1150 70

In the present study we have compared the immunophenotypic characteristics of the CD56+lo and CD56+hi NK-cell subsets in a group of normal healthy adults. Our results show that CD56+hi NK-cells display greater light-scatter properties than CD56+lo NK-cells at the same time they have higher levels of CD25 and CD122 IL-2 chains, together with a higher reactivity for HLA-DR and CD45RO and lower levels of CD45RA, supporting that, as opposed to the majority of the CD56+lo population, CD56+hi NK-cells might correspond to a subset of activated circulating NK-lymphocytes. Higher expression of the CD2 and CD7 costimulatory molecules found for the CD56+hi NK-cells would support their greater ability to respond to various stimuli. In addition, CD56+hi NK-cells expressed higher levels of several adhesion molecules such as CD2, CD11c, CD44, CD56, and CD62L compared to CD56+lo NK-cells, supporting a particular ability of these cells to migrate from blood to tissues and/or a potential advantage to form conjugates with target cells. Interestingly, CD56+lo and CD56+hi NK-cells showed a different pattern of expression of killer receptors that might determine different activation requirements for each of these NK-cell subsets. For instance, absence or low levels of CD16 expression might explain the lower antibody-dependent cytotoxicity activity of CD56+hi NK-cells. On the other hand, the virtual absence of expression of the CD158a and NKB1 immunoglobulin-like and the greater reactivity for the CD94 lectin-like killer receptors on CD56+hi in comparison to CD56+lo NK-cells might determine different MHC-class I specificities for both NK-cell subsets, a possibility that deserves further studies to be confirmed.
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PMID:Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK-cell subsets and its impact on the understanding of their tissue distribution and functional properties. 1177 57

We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human gammadelta-T cells. Here we show that gammadelta-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rbeta1); in contrast, gammadelta-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rbeta1. Next we show that gammadelta-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor alpha chain (IL-2Ralpha/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosis-sensitive gammadelta-T cells are shown to persist in their expression of IL-2Ralpha/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosis-resistant, but not apoptosis-sensitive, gammadelta-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Ralpha chain on apoptosis-resistant gammadelta-T cells, compared to apoptosis-sensitive gammadelta-T cells. The biological and clinical implications of these findings are discussed.
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PMID:Down-regulation of IL-2 receptor alpha (CD25) characterizes human gammadelta-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12. 1180 26

We constructed a chimeric molecule, composed of the T-cell receptor (TCR)-zeta chain fused to the extracellular domains of a prototypical allogeneic major histocompatibility complex (MHC) class I molecule, Dd, to assess whether such a construct could affect Dd allospecific responses in vitro and in vivo. To generate cytotoxic T lymphocytes (CTLs) expressing the construct, Dd-zeta was targeted to lymphocyte populations in transgenic mice by placing its expression under control of the CD2 promoter. In response to ligation of Dd, lymphocytes from transgenic mice expressing high levels of Dd-zeta are activated to proliferate and kill cells binding to Dd, despite the near total loss of CD8+ T cells in these mice. Thus, the Dd-zeta cytolytic cell was found not to be a conventional CD8+ CTL, but rather an unusual T lineage cell (CD3-CD5+Thy1.1+) that lacked alphabeta or gammadelta TCRs, as well as CD4 and CD8 coreceptors, but expressed surface markers strikingly similar to memory CTLs, including CD44, Ly-6C, and CD122. These cells originate in the thymus and potently veto responses to Dd in vitro. Lacking TCRs, these veto cells are unlikely to mediate graft-versus-host disease (GVHD) and thus may be useful as a cellular therapy for therapeutic deletion of alloreactive T cells in the settings of graft rejection and GVHD.
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PMID:Signaling through MHC in transgenic mice generates a population of memory phenotype cytolytic cells that lack TCR. 1258 13

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.
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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

Adult T-cell leukemia (ATL) develops in a small proportion of human T-cell leukemia virus I-infected individuals. Presently, there is no effective therapy for ATL. A murine model of ATL was produced by introducing leukemic cells (MET-1) from an ATL patient into nonobese diabetic/severe combined immunodeficient mice. The MET-1 cells are activated T cells that express CD2, CD3, CD4, CD25, CD122, and CD52. We evaluated the efficacy of Campath-1H (alemtuzumab; a humanized monoclonal antibody directed to CD52), alone and in combination with humanized anti-Tac (HAT) directed to CD25 (interleukin 2 receptor alpha) or with MEDI-507 directed to CD2. We observed that four weekly treatments with 4 mg/kg HAT significantly prolonged survival of MET-1-bearing mice. However, the survival of mice receiving 4 weeks of 4 mg/kg Campath-1H was significantly longer than that of the group receiving four weekly treatments with HAT (P < 0.001). Treatment with Campath-1H for 4 weeks led to a striking prolongation of the survival of MET-1 ATL-bearing mice that was comparable with that of tumor-free nontreated controls. Using Fc receptor (FcR) gamma(-/-) mice, we found that FcRgammas on polymorphonuclear leukocytes and monocytes are required for Campath-1H-mediated tumor killing in vivo. These results demonstrate that Campath-1H has therapeutic efficacy on ATL in vivo in that the life span of the Campath-1H treatment group was comparable with that of mice that did not receive a tumor or therapy. The main tumor killing mechanism with Campath-1H in vivo involves FcRgamma-containing receptors (e.g., FcRgammaIII) on polymorphonuclear leukocytes and macrophages that mediate antibody-dependent cellular cytotoxicity and/or trigger cross-linking induced apoptosis. This study provides support for a clinical trial of Campath-1H in the treatment of patients with T-cell leukemias and lymphomas.
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PMID:Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD52 monoclonal antibody, Campath-1H. 1455 36

Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56(+), NK cells in the absence of any clonal marker are present in the peripheral blood. In the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56(-) or expressed very low levels of CD56 (CD56(-/+dim) NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56(+) NK cells, CD56(-/+dim) NK cells were granzyme B(+), CD3(-), TCRalphabeta/gammadelta(-), CD5(-), CD28(-), CD11a(+bright), CD45RA(+bright), CD122(+), and CD25(-) and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56(-/+dim), they were CD11b(-/+dim) (heterogeneous), CD7(-/+dim) (heterogeneous), CD2(+) (homogeneous), CD11c(+bright) (homogeneous), and CD38(-/+dim) (heterogeneous). Moreover, CD56(-/+dim) NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56(-/+dim) NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56(-/+dim) showed a typical Th1 pattern of cytokine production (interferon-gamma(+), tumor necrosis factor-alpha(+)). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. In summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56(-/+dim)/CD11b(-/+dim) phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases.
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PMID:Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56-/+dim chronic natural killer cell large granular lymphocytosis. 1546 79


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