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)

Interleukin-4 (IL-4) counteracts a number of the direct effects of interleukin-2 (IL-2) on B-cells. We here summarize and extend our results, obtained in two different experimental systems, on the antagonism between these two major interleukins. IL-4 inhibits the effect of IL-2 on the proliferation as well as the differentiation of B-type chronic lymphocytic leukemia (B-CLL) cells. When B-CLL cells are activated by anti-mu Ab in the presence of IL-4, this latter enhances the expression of the p55 as well as the p70/75 chain of the IL-2 receptor. In contrast IL-4 profoundly suppresses the number of high affinity binding sites for IL-2 on in vitro activated B-CLL cells. Such a discrepancy between the suppression of IL-2 binding sites and the enhancement of each component of the heterodimeric IL-2 receptor, is as far as we know, yet undescribed. The interaction of IL-4 with its own receptors might influence the state of p55-p70/75 complex association or act on a third subunit of the IL-2 receptor. When used alone, IL-4 enhances the expression of other activation molecules by B-CLL cells: CD23, DR antigen. Similarly IL-4 can concomitantly enhance the specific response of normal B-cells while suppressing the action of IL-2. When normal human B-cells are specifically stimulated by an insolubilized antigen, IL-4 alone induces an expansion of the number of specific antigen-binding cells. In contrast IL-4 profoundly suppresses the generation of antigen-induced IL-2-dependent specific IgM antibody forming cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory effects of IL-4 on human B-cell response to IL-2. 210 12

The majority of CLLs are of B lineage derivation with about 5 per cent of cases of T lineage. Although morphologically resembling the small peripheral blood B cell, by virtue of the expression of B cell restricted and associated cell surface antigens, B-CLLs are not the neoplastic counterparts of normal resting B cells. Similar to the peripheral blood B cell, B-CLLs express CD19, CD20, CD21, CD24, CD40, CD44, CD45R, and sIgM/D. However, unlike peripheral blood B cells, B-CLLs generally do not express C3b complement receptor, LFA-1, or CD22. In addition, B-CLLs express the T cell associated antigen CD5, and a number of antigens induced on normal B cells following in vitro activation (B5, Blast-1, CD23). These findings support the hypothesis that B-CLLs are the neoplastic counterparts of one or more unique subpopulations of normal B cells. Normal CD5+ B cells, which phenotypically resemble B-CLL, are present in fetal lymphoid tissues and in small numbers in adults. Moreover, normal CD5+ B cells are present in increased numbers in patients with autoimmune diseases and a subset of normal in vitro activated B cells phenotypically resemble B-CLL. Similar studies into the state of differentiation of T-CLL cells suggest that although most cases resemble normal activated T helper cells, a significant number are the neoplastic counterparts of natural killer cells. Recent studies have examined the function of B and T cells in B-CLL. Although controversial, these studies suggest that the in vitro response to mitogens and cytokines of B-CLL cells is abnormal. T cell proliferation in B-CLL is depressed due to an inability to produce sufficient T cell growth factor (IL-2) as well as a poor response to exogenous IL-2 possibly from ineffective IL-2 receptor expression. Purified populations of T helper and T suppressor cells demonstrate insufficient support of Ig production by normal B cells as well as excess suppression, respectively. These studies have further supported the previous hypothesis that the depressed cellular and humoral immunity in CLL is multifactorial with both abnormal B and T cell function.
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PMID:Immunobiology of chronic lymphocytic leukemia. 218 99

T cells from the peripheral blood of a T-cell chronic lymphocytic leukemia (T-CLL) patient, cultured in the presence of interleukin-2 (IL-2), were found to express the p19 structural core protein of the human T-cell leukemia/lymphoma virus (HTLV) and to release type C virus particles. Comparison of the T-CLL cell line with the original leukemic T cells revealed that both the fresh and the proliferating T-CLL cells were pleomorphic cells that showed a convoluted nucleus and formed rosettes with sheep erythrocytes (E-rosettes). They were reactive with the monoclonal antibodies OKT1, OKT4 and OKT11, but not with OKT3, OKT6 or OKT8, indicating that they were mature T cells but that they differed from normal T cells in their lack of reactivity with OKT3. In addition they did not bind peanut agglutinin or OKM-1, and were negative for Epstein-Barr nuclear antigen, surface immunoglobulin, non-specific esterase activity of Fc- or complement receptors. Part of the fresh T-CLL cells reacted with a monoclonal antibody recognizing HLA-DR antigens (p29, 34) (36%) and with anti-Tac (62%), a monoclonal antibody directed at the IL-2 receptor, indicating that the T-CLL cells were partially activated already in vivo. After culture in vitro all proliferating T-CLL cells expressed HLA-DR and Tac antigens. The fresh T-CLL cells were found to be defective in cell-mediated lympholysis (CML) generated in mixed lymphocyte culture (MLC), antibody-dependent cellular cytotoxicity (ADCC) and lectin-dependent cellular cytotoxicity (LDCC). In addition they failed to exhibit natural killer (NK) cell activity against targets that are usually very susceptible to lysis, such as K562, but were able to kill two tumor-derived cell lines, the melanoma NKI-4 and the neuroblastoma CHP-100. The same pattern of selective killing was observed using the proliferating T-CLL cells as effectors, or cloned T-CLL cultures obtained from them by limiting dilution procedures. Therefore, it was concluded that the T-CLL cells represented a clonal expansion of neoplastic T cells that retained their phenotype and cytotoxic properties after culture in vitro.
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PMID:Phenotypic and functional characterization of HTLV positive neoplastic T cells cultured with interleukin-2--I. Retention of morphology, phenotype and selective cytotoxic properties in long term culture. 632 59

We describe a case of hemophagocytic syndrome (HPS) associated with CD8-positive T-cell chronic lymphocytic leukemia (CD8 + T-CLL). A 68-year-old man with CD8 + T-CLL presented with fever, progressive pancytopenia, and lymphadenopathy. Laboratory findings showed a hyper-ferritinemia, abnormalities of coagulation tests, and liver and renal dysfunction with hypoproteinemia. He did not respond to any treatments and died of respiratory failure 10 days after the admission and 14 months after the onset of CD8 + T-CLL. Pathological findings of the autopsy demonstrated infiltration of CD8 + T-CLL cells in multiple organs along with the increase of histiocytes with prominent hemophagocytosis. Serum concentration levels of IL-6, soluble IL-2 receptor and VEGF were all elevated at admission. These findings revealed that he had a secondary HPS. It was suggested that HPS should be considered in patients with an unexplained cytopenia and a fever during the clinical course of CD8 + T-CLL.
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PMID:Hemophagocytic syndrome associated with CD8 positive T-cell chronic lymphocytic leukemia. 1506 Dec 21