Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported liver-specific interferon (IFN) alpha/beta production by murine Kupffer cells that was not observed with other tissue macrophages incubated in the absence of stimulators such as IFN gamma or lipopolysaccharide (LPS). Consequently, while interleukin-2 (IL-2) alone induced pronounced lymphokine-activated killer (LAK) activity from splenocytes, combination of anti-IFN alpha/beta antibody with IL-2 was required to generate significant LAK activity from nonparenchymal liver cells. This endogenous IFN alpha/beta production by Kupffer cells was not induced by LPS because (a) addition of polymyxin B did not abolish the positive effects of anti-IFN alpha/beta antibody on nonparenchymal liver cells, and (b) similar results were obtained when comparing the responses of LPS-responsive C3HeB/FeJ and LPS-hyporesponsive C3H/HeJ mice. The possibility of hepatotropic infection was also ruled out in that anti-IFN alpha/beta antibody enhanced hepatic but not splenic LAK cell induction in vitro in both conventional and germ-free C3H/HeN mice. IFN alpha/beta played an autoregulatory role by down-regulating the production of IL-1 and tumor necrosis factor alpha by Kupffer cells. However, the augmenting effect of anti-IFN alpha/beta antibody on LAK induction from non-parenchymal liver cells was not mediated through an increase in the level of either IL-1 or TNF alpha, as specific antisera against either cytokine did not abrogate this positive effect. Finally, flow-cytometry analysis showed that IFN alpha/beta significantly diminished the expression of IL-2 receptor alpha chain, indicating an inhibition of LAK cell generation at a relatively early stage of induction.
 ...
PMID:Endogenous interferon alpha/beta produced by Kupffer cells inhibits interleukin-1, tumor necrosis factor alpha production and interleukin-2-induced activation of nonparenchymal liver cells. 175 31

The antigen-dependent proliferative response of the Ia- T lymphocyte population in peritoneal exudate cells (PEC) of C3H/HeN mice immunized with horse red blood cells (HRBC) was examined by determining the uptake of tritiated thymidine ([3H]TdR) into the cells in vitro. Both the antigen and accessory cell population, which was either macrophages or B lymphocytes that had been prepared from the PEC or spleen of unimmunized mice, were necessary for the proliferative response of the Ia- T cell population and also the production of IL-2 by the Ia- T cells, but the Ia- T cell population could proliferate in the absence of antigen and accessory cells, if IL-2 was present. The IL-2-dependent proliferation of the Ia- T cells was augmented in the presence of macrophages, but not B cells. The Ia- T cells that had been treated previously with anti-IL-2 receptor (IL-2R) antibody showed no response to IL-2 in the presence or absence of B cells, but responded to IL-2 in the presence of macrophages. Direct contact of the Ia- T cells with macrophages seemed to be necessary for augmentation of the proliferative response of the Ia- T cells to IL-2 because the separation of these cell populations by a membrane filter in a Marbrook type culture vessel resulted in poor augmentation of the response. Cell-associated IL-1 did not participate in the augmentation because paraformaldehyde-treated macrophages did not help the response. When the Ia- T cells had been previously treated with complement and anti-asialo GM1 antibody, the IL-2-dependent proliferative response was not affected, but the augmentation of the response by macrophages was blocked. Previous treatment of the cells with anti-L3T4 antibody diminished the response to IL-2, but did not affect the augmentation of the response by macrophages. Pretreatment of the cells with anti-Thy-1.2-antibody reduced the response to IL-2 and the augmentation by macrophages. Therefore, we concluded that there are at least two populations, capable of responding to IL-2 in the immune Ia- T cell population; one with L3T4 surface antigen and another with asialo GM1 antigen. The response of the latter cells, but not the former, to IL-2 is augmented in the presence of macrophages.
 ...
PMID:Macrophage-dependent and B-cell-dependent proliferative T-cell populations in the peritoneal exudate cells of immunized mice. 179 35

Two signals are required for the in vitro activation of Lyt2+ T suppressor cells (Ts) from mice tolerized with 2,4-dinitrobenzene sulfonate (DNBS) to produce soluble suppressor factors (SSF) which suppress the transfer of contact sensitivity to dinitrofluorobenzene (DNFB). Recognition of DNP/class I MHC (signal one) stimulates the Ts to synthesize SSF. Release of SSF requires a soluble mediator (signal two) produced by the interaction of L3T4+ T cells from tolerant mice with I-A on metabolically functional cells in the DNP-presenting cell population. The purpose of this study was to examine the nature of this second Ts activation signal. Coculture of tolerant spleen cells and glutaraldehyde-fixed (Glu-) DNP-labeled spleen cells (DNP-SC) resulted in the synthesis but not release of SSF. Addition of either IL-1 or IL-2 to these cultures induced SSF release. Treatment of such cultured cells with the anti-murine IL-2 receptor antibody PC 61.5.3 blocked the IL-2- and IL-1-stimulated release of SSF. Release of SSF was also blocked when tolerant cells were cultured with (unfixed) DNP-SC in the presence of a monoclonal anti-IL-2 antibody. IL-2 but not IL-1 was able to stimulate the Ts to release synthesized SSF in the absence of L3T4+ TH activity. First, addition of IL-2 to cocultures of tolerant cells and DNP-presenting I-A- cells induced release of the synthesized SSF, whereas addition of IL-1 did not. Second, IL-2 also stimulated SSF release in cocultures of L3T4+ T cell-depleted tolerant cells and Glu-DNP-SC, whereas IL-1 did not. Tolerant cells pretreated with IL-2 and then washed were able to synthesize and release SSF upon culture with Glu-DNP-SC. Pretreatment of tolerant cells with IL-1 did not stimulate SSF release upon subsequent culture with Glu-DNP-SC. These results indicate that the Lyt2+ Ts from DNBS-tolerant mice express IL-2 receptors and IL-2 is the lymphokine which induces the Ts to release synthesized SSF. Thus, IL-2 provides a differentiative signal during the functional activation of these regulatory T cells.
 ...
PMID:Soluble factors in tolerance and contact sensitivity to DNFB in mice. X. IL-2 is the activation signal mediating release of synthesized suppressor factor. 182 30

Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, in nanomolar concentrations blocks proliferative responses of cultured human, mouse and rat T lymphocytes and B lymphocytes to mitogens or in mixed lymphocyte reactions. The inhibitory effect of MPA on lymphocyte proliferation is reversed by addition to culture media of deoxyguanosine or guanosine but not by addition of deoxyadenosine or adenosine. The findings suggest that the principal mechanism of action of low concentrations of MPA is depletion of deoxyguanosine triphosphate which is required for DNA synthesis. In immunosuppressive doses, MPA does not affect the formation of IL-1 by LPS-activated human peripheral blood monocytes. Unlike cyclosporin A and FK-506, MPA does not inhibit the formation of IL-2 and the expression of the IL-2 receptor in mitogen-activated human T lymphocytes. MPA suppresses mixed lymphocyte reactions when added 3 days after their initiation. These findings suggest that MPA does not inhibit early responses of T and B lymphocytes to mitogenic or antigenic stimulation but blocks the cells at the time of DNA synthesis. The cytostatic effect of MPA is more potent on lymphocytes than on other cell types, such as fibroblasts and endothelial cells. MPA also inhibits antibody formation by polyclonally activated human B lymphocytes. MPA is an immunosuppressive agent reversibly inhibiting proliferation of T and B lymphocytes and antibody formation, with a profile of activity different from that of other immunosuppressive drugs. Human T and B lymphocytic and promonocytic cell lines are highly sensitive to the antiproliferative effects of MPA, whereas the erythroid precursor cell line K562 is less susceptible. The effect of MPA on cells of the monocyte-macrophage lineage could exert long-acting anti-inflammatory activity. MPA or analogues may have therapeutic utility in diseases such as rheumatoid arthritis, for prevention of allograft rejection and in lymphocytic or monocytic leukaemias and lymphomas.
 ...
PMID:Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion. 182 93

The extracellular matrix (ECM) is composed of a number of macromolecules that promote cell adhesion, cell migration, and differentiation. Receptors for these molecules have been identified and belong to a superfamily of cell surface proteins, collectively known as the integrins. In this study, we show that the matrix protein fibronectin (FN) acts synergistically with immobilized anti-CD3 antibody to promote proliferation of total human peripheral blood lymphocytes (HPBL) in the absence of exogenous IL-2. Proliferation was inhibited by both the alpha 5 beta 1 and alpha 4 beta 1 recognition peptides. ARG-GLY-ASP (RGD), and GLU-ILE-LEU-ASP-VAL-PRO-SER-THR (EILDVPST), respectively. Expression of CD25 (IL-2 receptor) was significantly higher on cells cultured on anti-CD3 and FN, indicative of T-cell activation. Additionally, cells cultured on immobilized anti-CD3 and FN for 3 days showed increased adhesion to FN and increased forward light scatter/side scatter profile. Synthesis of both IL-1 and to a lesser extent IL-2 was elevated in supernatants from cultures containing both anti-CD3 and FN. These data are consistent with published reports which demonstrate that ECM proteins can act as costimulants of lymphocyte proliferation. Finally, our results show that cells cultured on anti-CD3 antibody and FN have an activated phenotype and that cytokines may be involved in this process.
 ...
PMID:Fibronectin augments anti-CD3-mediated IL-2 receptor (CD25) expression on human peripheral blood lymphocytes. 182 61

The ability of adherent and nonadherent peripheral blood mononuclear cells (PBMC) from forty patients with schistosomiasis to produce IL-1 and IL-2 was studied. The results indicated that ConA-stimulated nonadherent-PBMC from patients exhibited a decreasing ability to produce IL-2 compared with controls (P less than 0.001), and that their ConA-activated blast cells expressed a smaller number of cell surface IL-2 receptor since IL-2 adsorption to the patient cells was lower than that to the normal cells (P less than 0.01). On the other hand, IL-1 production by LpS-stimulated adherent-PBMC from the patients was in agreement with that from the normal controls (P greater than 0.05). From above results, it seems that human organism following infection of Schistosoma japonicum might display a sort of suppressive phenomenon in the production of and the response to IL-2.
 ...
PMID:[Observation on the production of interleukin-1 and interleukin-2 and response to interleukin-2 in patients with schistosomiasis]. 190 57

Subcutaneous injection of human recombinant interleukin 1 (IL-1) beta was given to 9 patients with urological malignancies (5 renal cell carcinoma, 2 bladder carcinoma, 1 renal pelvic tumor, and 1 testicular tumor), at an initial dose of 1 x 10(4) units on days 1 and 2, and there after weekly for 4 weeks. The dose was increased by 1 x 10(4) units weekly up to final dose of 4 x 10(4) units. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in week 2 and week 4, and lymphokine-activated killer (LAK) activity against Daudi cells was measured using 4 hr 51Cr-release assay, after incubation with human recombinant interleukin 2 (IL-2) of 50 units/ml for 72 hours. Proliferation of lymphocytes was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 hours. IL-1 beta increased the number of peripheral blood granulocytes and lymphocytes, but did not increase the numbers of monocytes and platelets. IL-1 beta significantly augmented IL-2-induced LAK activity in vitro, but this augmentation was neither accompanied by the increase of IL-2 receptor-positive cell ratio in peripheral blood lymphocytes nor enhancement of IL-2-induced proliferation of lymphocytes. Administration of IL-1 beta increased LAK activity of the patients, despite the fact that IL-1 beta did not increase LAK activity in vitro. The result suggests that IL-1 beta-stimulated LAK activity may be mediated by the induction of some cytokines in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effects of recombinant interleukin 1 beta on peripheral blood cells and induction of lymphokine-activated killer activity in patients with urological malignancies]. 192 Oct 14

The ability of fetal and young adult CD4-CD8- thymocytes to proliferate in chemically defined (serum-free) medium in the presence and absence of IL-2 was examined. Dissociated thymocytes from day 15 and older fetal mice proliferated in vitro in the presence but not the absence of IL-2. The degree of proliferation was increased by including IL-1 with the IL-2. Inclusion of IL-1 in cultures of fetal thymocytes was associated with an increase in the number of IL-2 receptor positive cells, relative to cultures containing IL-2 alone. Although unfractionated thymocytes failed to proliferate in chemically defined medium, CD4-CD8- cells purified from thymic cell suspensions from young adult mice from several inbred strains proliferated to a limited extent in the absence of added cytokines. Proliferation was augmented 40-100 fold by inclusion of IL-2 in cultures. IL-1 stimulated some proliferation by young adult CD4-CD8- cells, but, unlike the effect of IL-1 and IL-2 on fetal thymocytes, combination of IL-1 with IL-2 did not have a notable additive effect on IL-2 induced proliferation. Proliferation stimulated by both IL-1 and IL-2 was completely abrogated by inclusion of anti-IL-2 receptor antibody in the cultures. Thymocytes from F1 progeny of inbred strains of mice proliferated to a greater extent in the absence of IL-2 than did thymocytes from either parent strain, although the response to IL-2 was not significantly different. The data demonstrate that both fetal and adult CD4-CD8- thymocytes area capable of proliferating in response to IL-2 in vitro, suggesting that, as is the case during antigen specific responses by mature T cells, IL-1 and IL-2 cooperate to stimulate T cell proliferation during development in vivo.
 ...
PMID:Murine CD4-CD8- thymocytes are stimulated by interleukin-2 to proliferate in vitro in chemically defined medium. 192 87

Tripterygium wilfordii Hook F (TWH) is a vine-like plant that grows in a wide area of south China. An alcohol extract of this plant known as T2 has been suggested to be effective in the treatment of rheumatoid arthritis (RA). To examine the mechanism by which this herbal remedy might be effective in RA, the capacity of T2 to alter human immune responsiveness in vitro was investigated. Human peripheral blood mononuclear cells were obtained from normal adults and separated into purified populations of monocytes, T cells, and B cells. T2 at 0.1-1 micrograms/ml inhibited antigen- and mitogen-stimulated proliferation of T cells and B cells, interleukin-2 (IL-2) production by T cells, and immunoglobulin production by B cells. T2 did not affect IL-2 receptor expression by T cells, IL-1 production by monocytes, or the capacity of monocytes to present antigen. Inhibition could not be accounted for by nonspecific toxicity. These results support the conclusion that T2 exerts a powerful suppressive effect on human immune responses. This action might account for its therapeutic effectiveness in RA.
 ...
PMID:Effect of an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F on human immune responsiveness. 193 Mar 17

Very Little is known about the immunological attributes of human endothelial cells. In this study, we performed immunologic phenotypic analysis of cultured human dermal microvascular endothelial cells in comparison with human umbilical vein endothelial cells and examined the ability of various biologic response modifiers to alter the phenotypes. Using FACS analysis, both types of the cells appear to lack many of the cell surface markers of immunologically proficient cells, E.G. OKT4, OKT8, Leu7, FcIgG receptor, complement receptors, IL-2 receptor and HLA-Dr, but they possess beta 2-microglobulin and DAF. HLA-Dr antigens can be induced on both types of endothelial cells by gamma-IFN in a dose and time dependent manner. Both types of endothelial cells possess several kinds of Cell Adhesion Molecules (CAMs), such as ICAM-1, CD44, LFA-3, but not LFA-1 or CD2. ICAM-1 but not LFA-3 or CD44 can be upregulated by exposure of both types of endothelial cells to gamma-IFN, IL-1 and TNF. These data suggest that endothelial cells of the dermal microvasculature may play central roles in a variety of different cutaneous inflammation.
 ...
PMID:[Immunophenotypic analysis of human endothelial cells]. 197 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>