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)

Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell induction. The target cells utilized for assay were a human leukemia cell line K562, a human renal carcinoma cell line KU-2, autologous normal kidney tissues and autologous renal cell carcinomas. Culture supernatant of peripheral blood lymphocytes (PBL) and OK-432 (designated as OK conditioned medium or OK-CM) demonstrated enhanced cytotoxicity of fresh PBL against these target cells. Killer cell activity against autologous cancer cells could be also induced from PBL of renal cell carcinoma patients. Pretreatment of PBL with IFN-gamma revealed synergistic effect of OK-CM on killer cell induction. OK-CM derived from patients was shown to contain IL-2 activity as well as high titer of interferon. Neutralizing monoclonal antibody against IFN-gamma and IL-2 receptor demonstrated reduction of cytotoxicity. These results suggested potential benefit of sequential use of IFN-gamma and OK-432 for the treatment of metastatic renal cell carcinoma.
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PMID:Combination therapy for renal cell carcinoma using IFN-gamma and OK-432: in vitro study. 211 48

From 20 patients with ovarian carcinoma (4 with stage I and 16 with stage III disease), we obtained peripheral blood mononuclear cells (MNC) from each, tumor-associated MNC from 9, and ascitic MNC from 6. These cells were stimulated with interleukin 2 (IL-2), and radioactive chromium-release cytotoxicity assays were used to evaluate the lymphokine-activated killer (LAK) activity against autologous tumor cells and two natural killer-resistant cell lines. The LAK response was consistently better with control peripheral blood MNC than with patient-derived MNC against all targets. However, within the ascitic MNC population, LAK activity against two cell lines (Daudi and OVCAR) was not statistically different from that of the control MNC. Phenotypic analysis of the ascitic MNC with monoclonal antibodies and flow cytometry revealed an activated population (IL-2 receptor-positive) characterized by predominantly monocytes/macrophages and T cells. In addition, the peripheral blood LAK activity for patients with stage I disease was statistically better against each target than that from patients with stage III disease. These results suggest an immunosuppressive effect directly related to tumor burden. Except perhaps for the ascitic MNC, autologous MNC do not appear to be effective LAK sources. Follow-up of the stage III patients revealed no difference in 2-year survival associated with in vitro LAK response.
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PMID:Effector function of lymphokine-activated killer cells and cytotoxic T lymphocytes in ovarian epithelial carcinoma. 238 35

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
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PMID:Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. 815 60

The immune system of patients with head and neck cancer is frequently depressed. Serum inhibitory factors and immune cell dysfunction are known contributors to this depression, but their relative roles are unclear. We have examined these factors to determine whether a common pathway is involved. Is the defect an unresponding "switched-off cell" or is it a remedial defect responsive to the removal of serum inhibitory factors and/or to lymphokine restoration? Immune tests were performed in 66 patients with high-stage head and neck cancer. Serum inhibitory factors were measured by incubation of heat-inactivated serum (10%) with phytohemagglutinin (PHA)-stimulated lymphocytes or natural killer (NK) cells using the K562 assay. Lymphokine-activated killer (LAK) cell cytotoxicity was measured (in the presence/absence of serum) using chromium 51-labeled Raji tumor cells cultured 5 days with interleukin-2 (IL-2) (100 or 1,000 U/mL) and/or interferon-alpha (INF-alpha) (100 U/mL). IL-2 receptors, CD25 or p55 (low affinity) and p75 (high affinity), were measured by flow cytometry through fluorescence-activated cell sorter analysis. Serum inhibitory factors were detected in more than 50% of the patients. Head and neck cancer sera significantly inhibiting the normal lymphocyte response to PHA (11 of 22 patients), as well as significantly inhibiting the NK response of normal lymphocytes and the functional expression of the IL-2 receptor. LAK cell function at low-dose IL-2 was depressed in 45% of the patients (9 of 20) and was restored by increased IL-2 (1,000 U/mL) or a combination of IL-2 and INF-alpha. Twenty-five percent of the patients were unresponsive to maximum lymphokine stimulation. Half of the patients had depressed expression of the low-affinity IL-2 receptor (CD25). The cause of immune depression in patients with head and neck cancer is multifactorial and is related to serum inhibitory factors, as well as to inherent cellular defects. Based on these data, we would suggest a therapeutic approach in selected patients that includes the removal of serum inhibitory factors by plasmapheresis and restoration of cellular defects by combined IL-2 with or without INF-alpha.
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PMID:Contribution of serum inhibitory factors and immune cellular defects to the depressed cell-mediated immunity in patients with head and neck cancer. 821 99

We have evaluated the effects of chromium extract on the release by peripheral blood mononuclear cells (PBMCs) of cytokines favouring bone resorption. Furthermore, we have evaluated whether the chromium effects could be correlated with the activation and proliferation of PBMCs. Cell cultures were maintained in serum-free medium (AIM-V), in order to avoid the interference of exogenous growth factors. Increasing concentrations of chromium extract, ranging between 3 and 100%, were added to culture medium. Cytokine release (IL-1beta, TNFalpha, IL-6, GM-CSF and IFNgamma) was assessed on both PBMCs cultured with AIM-V only (unstimulated PBMC) and PBMCs cultured with AIM-V plus phytohaemagglutinina (PHA-stimulated PBMC). The activation and proliferation of PBMCs were evaluated by assessing DNA synthesis and soluble IL-2 receptor release, in order to determine whether an IL-2-dependent immune response can be induced by chromium. Our results show that in unstimulated PBMCs chromium ions slightly increased the release of pro-inflammatory cytokines, such as TNFalpha and IL-6, even though the increase is not significant. On the contrary, the different concentrations of chromium extract significantly inhibited the response to PHA stimulation, as shown by the decrease in IL-6 and sIL-2r release, and by the influence on cell viability and DNA synthesis. Both these effects are undesirable and support hypotheses on the biological effects of chromium. The continuous release of chromium from the implant could induce in PBMCs the release of bone-resorbing cytokines, which in the long term could be responsible for irreversible tissue damage. Moreover, chromium seems to inhibit the IL-2-dependent response of PBMCs, so that they are not able to trigger an efficient cell-mediated immune response.
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PMID:Effects of chromium extract on cytokine release by mononuclear cells. 967 77

A previously undefined phenotype of CD8(+) cells that appears to represent in vivo activated CTL precursors (CTLP*) has been identified in the spleens of C57Bl/6 mice responding to a P815 tumor allograft. This population was first evident by the transient expression of very high levels of CD28 and CD44 on day 5 of the allograft response and reached maximal levels on days 7 and 8 before declining on day 9. A transient increase in CD69 expression was also observed on these cells on day 5. In contrast, CTL effectors (CTLE), identified by their CD8(+)CD44(hi)CD62LloCD45RBlo phenotype, were not appreciably detected in the spleen until day 8 and reached maximal levels on day 10. Further characterization of CTLP* on day 7 revealed that they represented blasting cells by increased light scatter and also expressed very high levels of CD54 but not CD122, CD152, or CD154. In addition, the cells had already up-regulated CD49d, asialo GM1, CD11a, and CD95L, and down-regulated their expression of CD62L. A small percentage of these cells also expressed CD25. Day 7 CTLP* sorted on the basis of their CD44(xhi) and CD54(xhi) phenotype did not exhibit cytolytic activity in a standard chromium release assay but became cytotoxic when they were cultured in the presence of exogenous murine IL-2 for 5 days. Granzyme B activity, however, was detected in CTLP* on day 7 at levels equivalent to CTLE on day 10. In order to establish a potential precursor relationship between CTLP* and CTLE, mice were treated with various doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a chemical that has been shown to dose-dependently suppress the in vivo generation of CTLE to P815 tumor cells by altering an early stage of CTLP activation. Results indicated that CTLP* were suppressed by TCDD on day 7 to the same degree that CTLE were suppressed on day 10. Importantly, for controls and for all doses of TCDD, there were approximately 12.5 CTLE on day 10 for every CTLP* detected on day 7. These results suggested that TCDD acted identically across all doses to inhibit the early stages of activation of CTLP but did not affect the final stages of differentiation and expansion to CTLE. This interpretation supports the previous observation that TCDD exposure had to occur within the first 3 days of the allograft response in order to induce suppression of CTLE activity. Taken together, these results support the conclusion that in vivo activated CTLP can be identified by their unique expression of very high levels of CD44, CD28, and/or CD54 prior to their full maturation and clonal expansion to functional CTLE.
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PMID:Novel phenotype associated with in vivo activated CTL precursors. 1007 61