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)

Activation of resting T cells induces synthesis of IL-2 and expression of its specific high-affinity receptor. We have proposed a multichain model for the high-affinity IL-2 receptor in which both a 55 kDa IL-2-binding peptide identified by the anti-Tac monoclonal antibody and a 70/75 kDa IL-2-binding peptide are associated in a receptor complex. The IL-2 receptor is proving to be an extraordinarily versatile therapeutic target, since it is expressed by the abnormal T cells in patients with certain lymphoid malignancies or autoimmune disorders and in individuals rejecting allografts, whereas it is not expressed by normal resting cells. Specifically, HTLV-I-associated adult T-cell leukaemia cells constitutively express large numbers of IL-2 Tac receptors. A 42 kDa tax protein encoded predominantly by the pX region of HTLV-I may play a part in directly or indirectly increasing the transcription of the 55 kDa Tac IL-2 receptor gene. To exploit the fact that IL-2 receptors are present on abnormally activated T cells but not on normal resting cells, clinical trials have been initiated involving patients with Tac-expressing haematologic malignancies. These patients are being treated with unmodified anti-Tac, with anti-Tac conjugated to truncated PE toxin, with isotopic (212Bi and 90Y) chelates of anti-Tac and with recombinant 'humanized' anti-Tac. Thus, the clinical application IL-2 receptor-directed therapy represents a new perspective for the treatment of certain neoplastic diseases.
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PMID:IL-2 receptor expression in the haematologic malignancies: a target for immunotherapy. 270 34

Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA.
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PMID:Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. 278 15

We examined the expression of cell-surface interleukin-2 (IL-2) receptor (Tac antigen) on peripheral blood leukemic cells and measured soluble IL-2 receptor p55(alpha) chain (sIL-2R) levels in sera from chronic myelogenous leukemia (CML) patients with blastic crisis. Flow cytofluorometric analysis performed by dual immunofluorescence in three cases demonstrated coexpression of Tac antigen with myeloid (CD13, CD14, or CD33) or lymphoid (CD10) antigen on significant proportions of peripheral blood leukemic cells. Radiolabeled IL-2-binding assay demonstrated the specific IL-2 binding sites in three cases examined. The exogenous IL-2, however, failed to induce proliferative response. A myeloid cell line, Yut-K3, established from peripheral blood leukemic cells from a CML patient with blastic crisis, also expressed cell-surface Tac antigen and CD13 concurrently. SIL-2R assay showed that Yut-K3 released a detectable amount of sIL-2R in its culture supernatant. The serum sIL-2R levels were significantly elevated (range: 2,580 to 172,000 U/mL) in 12 CML patients with blastic crisis and were slightly elevated in ten patients in chronic phase (range: 250 to 820 U/mL) and in three in accelerated phase (range: 790 to 1,305 U/mL) compared with those in 24 normal controls (range: 70 to 695 U/mL, P less than .01). These results indicated that the leukemic cells from CML patients with blastic crisis expressed and released IL-2 receptor (Tac antigen). Longitudinal studies performed in three cases of CML with blastic crisis showed that the change of serum sIL-2R level was closely associated with that of the number of peripheral blood leukocytes and blasts, the percentage of blasts and serum LDH levels, also suggesting that the serum sIL-2R level is a useful clinical indicator of the leukemic cell burden in vivo.
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PMID:Elevated serum-soluble interleukin-2 receptor (Tac antigen) levels in chronic myelogenous leukemia patients with blastic crisis. 278 81

Skin biopsy specimens from normal skin and from 115 patients with benign dermatoses, pre- or pseudo-malignant disorders or malignant cutaneous lymphomas have been examined immunohistologically for expression of the Reed-Sternberg cell associated antigen CD30 detected by monoclonal antibodies Ki-1 and Ber-H2. The antibodies stained the atypical cells in lymphomatoid papulosis, a proportion of the neoplastic cells in some cases of mycosis fungoides and most of the neoplastic cells in six large cell anaplastic/pleomorphic non-Hodgkin's lymphomas. The lymphoid cells in all other specimens were Ki-1- and Ber-H2-negative. In all cases, expression of the Ki-1/Ber-H2 antigen was accompanied by expression of activation and proliferation associated markers (i.e., HLA-DR, IL-2 receptor, transferrin receptor and the Ki-67 nuclear antigen). These data indicate the value of antibodies Ki-1 and Ber-H2 in distinguishing between lymphomatoid papulosis and other types of pre- or pseudo-malignant disorders and support the view that lymphomatoid papulosis, Hodgkin's disease and some types of non-Hodgkin's lymphoma constitute a spectrum of related disorders, originated from activated lymphoid cells.
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PMID:Expression of a Hodgkin and Reed-Sternberg cell associated antigen (Ki-1) in cutaneous lymphoid infiltrates. 282 Mar 16

Cynomolgus monkeys and squirrel monkeys were inoculated with autologous lymphoid cell lines immortalized by and producing human T-cell leukemia virus type-I (HTLV-I) in order to serve as an animal model of adult T-cell leukemia (ATL). The autologous cell lines were established from peripheral blood mononuclear cells (PBMC) from each monkey by co-cultivation with lethally irradiated MT-2 cells producing HTLV-I. All of these cell lines, which had monkey karyotypes, grew continuously without addition of interleukin-2 (IL-2) and expressed virus-specific proteins of HTLV-I and IL-2 receptor. After inoculation with the autologous cell lines, specific antibodies against HTLV-I proteins could be detected in their plasma, and transformed HTLV-I-infected cells could be recovered from their peripheral blood for at least 6 months. However, no signs of ATL have been observed to data, i.e. 2 years after inoculation.
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PMID:Experimental inoculation of monkeys with autologous lymphoid cell lines immortalized by and producing human T-cell leukemia virus type-I. 287 91

Cocultivation of spleen cells, lymph node cells, and thymocytes of female Wistar-King-Aptekman rats with short-term cultured male adult T cell leukemia (ATL) cells in the presence of 5-bromo-2'-deoxyuridine (BudR) resulted in the establishment of rat lymphoid cell lines, TARS-1, TARL-2, and TART-1. Cytogenic analysis of the three cell lines showed a female rat karyotype with 42 chromosomes. The surface phenotypes of TARS-1 and TART-1 were those of rat T cells. TARL-2 was only positive for rat Ia and leukocyte common antigens and brain associated T antigen. The cell lines continuously produced a type C retrovirus, human T cell leukemia virus-I (HTLV-I) and expressed ATL-associated antigens. By using monoclonal antibodies for rat IL-2 receptors, FACS analysis demonstrated that three rat T cell lines unequivocally expressed rat IL-2 receptor. TARS-1 and TART-1 but not TARL-2 were transplantable into newborn syngeneic rats and nude mice. By injecting MMC-treated TARS-1 into newborn syngeneic rats, HTLV-I carrier rats were obtained which showed gradual increase of anti-ATLA antibody titer by aging. No evidence of leukemia nor malignant lymphoma were observed in those carrier rats. Adult rats immunized with these rat cell lines produced antibodies specific for HTLV-I. The biochemical analysis of the antigen that reacted with rat sera revealed that they are the HTLV-I specific polypeptides, p28, p24, p19 and p15.
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PMID:[Rat lymphoid cell lines producing human T cell leukemia virus-I]. 288 Jul 89

Interleukin-2 (IL-2) is a lymphokine synthesized by T cells following activation. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells following interaction of the antigen-specific T-cell receptor complex with appropriately processed and presented antigens. Anti-Tac, a monoclonal antibody that recognized the IL-2 receptor, has been used to purify the receptor. The recognized the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-Kd glycoprotein comprised of 272 amino acids including a single 19-amino transmembrane domain and a short intracytoplasmic domain composed of 13 amino acids at the carboxy terminus. Normal resting T cells and most leukemic T-cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen. In HTLV-I-infected cells, the 42-Kd long open reading frame (tat) protein encoded in part by the tat region of HTLV-I may act as a transacting 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 both unmodified and toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
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PMID:The interleukin-2 receptor on normal and malignant lymphocytes. 288 69

The surface of dendritic cells from mouse spleen, thymus, and epidermis has been compared with a panel of monoclonal antibodies and the FACS. A method was first developed to isolate populations of large, adherent, thymic dendritic cells that were greater than 90% pure. These were released by collagenase digestion and separated from adherent macrophages after overnight culture. Enrichment was based on the facts that most macrophages remained plastic adherent and rosetted strongly with antibody-coated erythrocytes. As in spleen, thymic dendritic cells were stellate in shape, had abundant class I and II MHC products, lacked many standard macrophage and lymphocyte markers, and actively stimulated the mixed leukocyte reaction. Most spleen and thymic dendritic cells could be lysed by the 7D4 mAb, to the low-affinity IL-2 receptor, and complement but the levels of 7D4 by FACS were low and sometimes not above background. Differences among dendritic cells from different tissues were noted with other mAb. Adherent dendritic cells from thymus all expressed the J11d "B cell" antigen and the NL145 interdigitating cell marker, but lacked the 33D1 spleen dendritic cell antigen. Eighty to ninety percent of spleen dendritic cells were J11d-, NL145-, 33D1+ but the remainder expressed the J11d+, NL145+, 33D1- thymic phenotype. The latter phenotype also was identical to that of epidermal Langerhans' cells. We postulate that the major 33D1+ cell in spleen represents a migratory stage in which dendritic cells are moving from tissues to lymphoid organs.
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PMID:The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. 291 Apr 99

Peripheral blood mononuclear cells from 27 pregnant women and 10 age-matched non-pregnant women were examined for monoclonal antibody-defined T cells, immunoregulatory T-cell subsets, natural killer cells, activated T cells and surface Ig+B lymphocytes using a fluorescence-activated cell sorter (FACS analyzer). The autologous mixed lymphocyte reaction (AMLR) and in vitro influence of interleukin 1 (IL-1) and interleukin 2 (IL-2) on the AMLR were also studied. No significant difference was observed in the proportions of Leu 3+ (helper/inducer phenotype) and Leu 2+ (suppressor/cytotoxic) T cells during all three trimesters of pregnancy and in post-partum period when compared to non-pregnant healthy control women. T cells expressing DR antigen (evidence of T-cell activation) were significantly increased during second trimester (P less than 0.02) and in post-partum period (P less than 0.05). However, Tac+ T cells (IL-2 receptor positive T cells, another but distinct marker for T cell activation) were normal throughout pregnancy and in the post-partum period. Leu 7+ (HNK 1+) lymphoid cells (containing a population of natural killer cells) were normal during all 3 trimesters of pregnancy but were increased during post-partum period. Surface Ig+B cells were comparable to control group throughout pregnancy and during post-partum period. The AMLR was significantly deficient (P less than 0.01) during first and third trimester of pregnancy. In vitro addition of purified IL-2 restored the AMLR to the baseline levels of the controls but the AMLR was still lower than the levels in controls with IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autologous mixed lymphocyte reaction (AMLR) in man. XVI. The AMLR and monoclonal antibody-defined T cell subsets and HNK 1+ natural killer cells in normal human pregnancy. 294 61

We have analyzed the effects of high doses of cyclophosphamide (Cy) on primary and secondary antitumor immune response against immunogenic (tum-) variants of Lewis lung carcinoma (3LL) treated in vitro with UV light. Normal mice and mice previously immunized with tum- clones wer inoculated i.p. with Cy (200 mg/kg body weight) and 24 h later challenged intrafootpad with tum- or parental 3LL cells. Cy treatment suppressed the primary immune response of normal animals and allowed the growth of tum- cells. In contrast, Cy-treated immune mice rejected the tumor challenge. The in vivo treatment with Cy decreased the total number of lymphoid cells in the spleens, as well as the proportion of B lymphocytes; however, it increased the percentage of both Lyt2+ and L3T4+ lymphocytes. Thus, the immunosuppressive effects of Cy on the primary antitumor response could not be attributed to elimination of major T lymphocyte subpopulations. Although the treatment of immune mice with Cy did not significantly impair their antitumor resistance, nor the proportion of Lyt2+ and L3T4+ lymphocytes in their spleens, the in vitro generation of cytotoxic T lymphocytes (CTL) was markedly reduced. After Cy treatment, the proliferative ability of spleen cells in response to interleukin-2 (IL-2) was substantially impaired. Using monoclonal antibodies to the IL-2 receptor, we found that Cy-treated T lymphocytes failed to fully express the IL-2 receptor following in vitro stimulation with irradiated tumor cells. In line with these findings, the in vitro generation of CTL was not restored by addition of recombinant IL-2 to the cultures. In vivo experiments using purified functional subsets of immune T cells showed that Lyt1+, but not Lyt2+ lymphocytes were able to transfer antitumor immunity in normal irradiated recipients. Therefore, since Ly1+ T lymphocytes were responsible for the antitumor resistance in vivo, the Cy-induced impairment of CTL generation did not affect the ability of immune mice to reject a secondary tumor challenge.
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PMID:In vivo resistance of secondary antitumor immune response to cyclophosphamide: effects on T cell subsets. 294 33


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