Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00082 (IL-2)
 29,198 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine helper T cells activated to sheep or horse erythrocyte antigens in vivo have been established as continuous cell lines in culture. T cells require the presence of a T-cell growth factor (TCGF) for continuous proliferation. TCGF purified from murine, rat, or human sources all stimulate murine T-cell growth. The T-cell mitogens concanavalin A and phytohemagglutinin do not stimulate cell proliferation in continuous T-cell lines. All cells that grow in the presence of TCGF express Thy-1 antigens. Helper activity of T-cell lines is both antigen specific and effective for syngeneic or F1 B cells. Supernates from T-cell lines do not contain antigen-specific or nonspecific helper factors. Although several T-cell lines have shown stable helper activity for greater than 50 wk in culture, other cell lines have shown a gradual decline in effector function. The procedure used to establish and maintain proliferation of T cells in culture should be suitable for the selection and growth of antigen-specific effector T cells from each subclass.
J Exp Med 1979 Dec 01
PMID:Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. 9 24

To investigate the role of peritoneal mesothelial cells in regulating hematopoiesis, as well as inflammation, healing, and tissue regeneration processes, long-term cultures of peritoneal mesothelial cells from human endocavitarian fluids were established. The purity of the cell population was assessed by morphologic and immunocytochemical criteria. Five peritoneal mesothelial cell cultures were analyzed for cytokine expression. Macrophage colony-stimulating factor (M-CSF), granulocyte-CSF (G-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6 transcripts were constantly but variably detected throughout the culture period, while granulocyte-monocyte-CSF (GM-CSF) expression started as the cell culture aged. No IL-2, IL-3, IL-4, IL-5, or IL-7 transcripts were detected in the same samples. Corresponding cytokine activities were detected in the supernatants of the cultures. Peritoneal mesothelial cells proliferated after the addition of exogenous IL-1 beta or IL-1 alpha, whereas the addition of recombinant GM-CSF, G-CSF, M-CSF, or IL-6 failed to trigger proliferation. IL-1 receptor type I transcripts were detected in peritoneal mesothelial cells. Moreover, IL-1 was able to upregulate the expression of the genes that code for G-CSF, GM-CSF, IL-1 alpha, and IL-1 beta in these cells. These data indicate that peritoneal mesothelial cells produce many cytokines and suggest that IL-1 is a regulatory molecule for peritoneal mesothelial cells.
Blood 1992 Dec 01
PMID:Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor [CSF], granulocyte-monocyte-CSF, macrophage-CSF, interleukin-1 [IL-1], and IL-6) and are activated and stimulated to grow by IL-1. 128 Apr 80

Stimulation of T-lymphocytes derived from some patients with common variable immunodeficiency (CVID) syndrome results in defective proliferation. The underlying mechanism is related to the inability of stimulated cells to secrete IL-2 while the expression of IL-2 receptor (IL-2R) is normal. We have identified a patient whose peripheral T-cells failed to proliferate and secrete IL-2 upon stimulation. The addition of recombinant IL-2 restored proliferation. The defect did not seem to be caused by accessory cell failure since the patient's adherent cells produced IL-1 and IL-6, and addition of allogeneic irradiated cells did not induce proliferation. Stimulation of CVID T-cells with phorbol esters and Ca2+ ionophore induced both IL-2 secretion and proliferation, indicating the absence of a defect in the transcription and/or translation of the IL-2 gene. The patient's T-cells expressed high levels of CD3. The majority of T-cells expressed the CD38 molecule which is normally found on thymocytes or activated T-cells but not peripheral blood T-cells and HLA-DR, another activation marker. However, CD25 (the IL-2R) and CD1, a marker of more immature thymocytes, were not expressed. Finally, the patient's cells were sensitive to an in vitro corticosteroid treatment. The possibilities that this patient's T-cells represent anergic T-cells or not fully matured thymocytes are discussed.
Clin Immunol Immunopathol 1992 Dec
PMID:An unusual T-cell surface phenotype in vivo correlates with the failure to proliferate and produce IL-2 in vitro in a patient with common variable immunodeficiency. 128 May 40

T lymphocytes are activated by interactions with antigens, lymphokines, and cell adhesion molecules. Tyrosine phosphorylation has been implicated as important in signaling through each of these pathways, but except for p56lck, a member of the Src family that associates with CD4 and CD8, the protein-tyrosine kinases involved have not been defined. We describe here a tyrosine kinase gene that we have designated itk (for IL-2-inducible T-cell kinase). The itk gene specifies a 72-kDa protein-tyrosine kinase that is related to members of the Src family but lacks two features characteristic of Src kinases: an N-terminal myristoylation consensus sequence and a regulatory tyrosine residue near the C terminus. Analysis of mouse tissues and cell lines indicates that itk is specifically expressed in the T-cell lineage, suggesting that the tyrosine kinase encoded by itk functions in a signal transduction pathway unique to T lymphocytes. On addition of IL-2 to responsive T cells, itk RNA increases in parallel with that of IL-2R alpha, implicating itk in T-cell activation.
Proc Natl Acad Sci U S A 1992 Dec 01
PMID:itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. 128 Aug 21

Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.
Clin Exp Immunol 1992 Dec
PMID:Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19). 128 Oct 55

The membrane potential of human PBMC was modulated in culture by isotonic high extracellular K+ (K+e), or the K+ channel blocker, charybdotoxin (ChTX), to determine the effect of depolarization on stimulated proliferation, IL-2 elaboration, and gene expression. In serum-free cultures, ChTX and high [K+]e induced a specific dose-dependent decrease in IL-2 production. ChTX inhibited proliferation of PBMC and purified T cells, decreased IL-2 elaboration 15 h after stimulation by 78.4 +/- 5.3% (n = 5), and decreased IL-2 mRNA steady-state levels by 80% between 8 and 10 h after stimulation. The IC50 for ChTX-inhibition of IL-2 elaboration and IL-2 mRNA were both 1 nM. Similarly, high [K+]e inhibited proliferation with an IC50 of 38.9 +/- 1.1 mM (n = 13), decreased IL-2 elaboration with an IC50 of 21.3 +/- 1.2 mM (n = 6), and decreased IL-2 mRNA steady-state levels with an IC50 of 18 mM. The sensitivities of both IL-2 production and proliferation to depolarization were substantially reduced by calcium, serum, and exogenous rIL-2. From these findings we conclude that membrane potential may contribute to the control of immune responsiveness in vivo.
J Immunol 1992 Dec 15
PMID:Evidence for voltage modulation of IL-2 production in mitogen-stimulated human peripheral blood lymphocytes. 128 Nov 85

We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.
J Immunol 1992 Dec 15
PMID:Murine B7 antigen provides a sufficient costimulatory signal for antigen-specific and MHC-restricted T cell activation. 128 Nov 87

The expression of membrane-associated forms of lymphotoxin (LT) and TNF were examined on cell lines of T, B, and myeloid origin, IL-2 dependent T cell clones, and peripheral blood lymphocytes. Inducible and constitutive patterns of surface LT expression were found on T cells as exemplified by the II-23.D7, a CD4+T cell hybridoma, and HUT-78, a T cell lymphoma. Phorbol ester induced surface LT expression on Ramos, an EBV transformed B cell line, but at a slower rate of appearance when compared to the II-23.D7. Secretion of LT was rapidly inducible by phorbol ester in II-23.D7 and also in HUT-78 but with slower kinetics; surface LT expression continued in both lines after secretion had ceased. Low levels of membrane TNF were transiently induced on II-23.D7 and HUT-78, but none was observed on Ramos. Peripheral blood monocytes and some myeloid tumor lines did not express surface LT. Several T cell clones expressed surface LT after Ag-specific stimulation, and expression persisted several days. Stimulation through the TCR or by IL-2 rapidly induced surface LT on resting peripheral T cells and CD56+ NK cells; pokeweed mitogen activation induced expression on CD20+ B cells. Consistent with previous results, immunoprecipitation with anti-LT mAb showed that LT was complexed with a distinct 33 kDa glycoprotein (p33) on cells that expressed surface LT, whereas secreted LT was not associated with p33. Surface and secreted modes of LT expression by activated T, B, and NK cells suggests that LT can be utilized as either a localized or diffusible mediator in immune responses.
J Immunol 1992 Dec 15
PMID:Expression of surface lymphotoxin and tumor necrosis factor on activated T, B, and natural killer cells. 128 Nov 93

We previously reported a dramatically increased number of macrophages in tumor-bearing mice. In this study, we investigated the involvement of CSF in that phenomenon. CSF-1 responding cells as macrophages precursors increased significantly in number in the spleens of tumor-bearing mice as compared with those in normal mice. Splenic cells and sera from the tumor-bearing mice respectively expressed CSF-1 in mRNA and serum protein levels, but failed to express the other CSF (granulocyte-macrophage-CSF or IL-3). Nonadherent splenic mononuclear cells (< 0.5% macrophages) from normal mice proliferated and differentiated into mature macrophages in culture within 7 days with recombinant mouse CSF-1 (rCSF-1). Both macrophages harvested from tumor-bearing mice and those activated in vitro with rCSF-1 expressed mostly Mac-1, -2 (and -3) Ag, showed yeast phagocytosis, produced IL-1 but not IL-2 or IL-3, and displayed potent cytotoxicity against NK cell resistant Meth-A tumor cells. These macrophages also expressed lipocortin I mRNA and secreted lipocortin I protein, and suppressed mitogenic responses of splenic lymphocytes. rCSF-1-activated macrophages derived from nonadherent splenic cells expressed both CSF-1 and CSF-1 receptor (c-fms) mRNA. Administration of rCSF-1 into normal mice induced hemopoietic and immunologic alternations similar to those observed in tumor-bearing mice. These results suggest that CSF-1 is involved in the dramatic increase of macrophages in tumor-bearing mice, possibly through an autocrine or paracrine loop.
J Immunol 1992 Dec 15
PMID:Role of colony-stimulating factor-1 in macrophage activation in tumor-bearing mice. 128 Nov 98

High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2R alpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n = 5, group I, controls), unmodified anti-Tac (n = 5, 1 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n = 4) were treated identically to those in group III with the exception that 5 micrograms/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2 +/- 0.5 days as compared with 13.8 +/- 2.1 days (P < 0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received 90Y-anti-Tac, with a mean graft survival of 45.0 +/- 11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with 90Y-anti-Tac had a mean graft survival of 49.2 +/- 2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with 90Y-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases.
Transplantation 1992 Dec
PMID:Prolongation of graft survival in primate allograft transplantation by yttrium-90-labeled anti-Tac in conjunction with granulocyte colony-stimulating factor. 128 66


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