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)

Because mice are more resistant than humans to the pathogenic effects of bacterial toxins, we used D-Galactosamine- (D-Gal) sensitized mice as a model system to evaluate potential toxic shock symptoms triggered by the superantigen staphylococcal enterotoxin B (SEB). We show that similar to endotoxin (lipopolysaccharide) [LPS], the exotoxin SEB causes lethal shock within 8 h in D-Gal-sensitized mice, inducing 100% and about 50% lethality with 20 and 2 micrograms SEB, respectively. The lethal shock triggered by the superantigen SEB is mediated by T cells, a conclusion based on the observation that T cell repopulation of SCID mice conferred sensitivity to SEB. Since CSA also conferred protection, the role of T cell-derived lymphokines in mediating lethal shock was evaluated. Within 30-60 min after SEB injection, serum tumor necrosis factor (TNF) levels peaked, followed immediately by interleukin-2 (IL-2). Serum-borne lymphokines were detected well in advance of signs of T cell activation, as assessed by IL-2 receptor expression of SEB-reactive V beta 8+ T cells. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody also conferred protection, indicating that it is TNF which is critical for initiating toxic shock symptoms. Taken together, this study defines basic differences between endotoxin (LPS)- and exotoxin (SEB)-mediated lethal shock, in that the former is mediated by macrophages and the latter by T cells. Yet the pathogenesis distal to the lymphokine/cytokine-producing cells appears surprisingly similar in that TNF represents a key mediator in inducing shock.
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PMID:T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. 173 Sep 29

Patients harboring a malignant brain tumor have been described as being highly immunosuppressed, as evidenced by reduced numbers of T cells and the decreased ability of their lymphocytes to produce interleukin-2 (IL-2). In order to determine whether an intrinsic abnormality exists in the T lymphocytes of glioma patients and to evaluate what role corticosteroids may play in glioma-associated immunosuppression, in vitro T cell proliferative function in the presence of recombinant IL-2 (rIL-2) was examined in age-matched groups of normal control subjects, steroid-free patients with glial tumors, steroid-dependent patients with glial tumors, and steroid-dependent patients with nonglial cerebral tumors. The results demonstrated that, when enriched T cell populations of all brain-tumor patients were stimulated with rIL-2 and phytohemagglutinin (PHA), there were no statistically significant differences between any groups. In contrast, when T cell populations were stimulated with mitogenic combinations of phorbol ester, calcium ionophore, and rIL-2, those from steroid-dependent patients with glial tumors had a significantly lower response than those from normal control subjects, suggesting that a population of T cells capable of responding to phorbol ester/ionomycin and not PHA stimulation is inhibited by corticosteroid therapy in glioma patients. In addition, T cells of four brain-tumor patient/age-matched control subject pairs were stimulated with either phorbol ester/ionomycin or PHA for 24 hours; three of the four patients expressed low-affinity IL-2 receptor levels as high or higher than their respective control subjects, suggesting that IL-2 receptor expression in these patients may be quantitatively normal once the T cell number is corrected. Taken together, these results show that the decreased PHA responsiveness that has been previously reported in lymphocytes of glioma patients is not due to a cellular abnormality within the potentially responsive cells, but rather reflects the reduced proportion of T cells within their peripheral blood which, as a consequence, reduces the level of IL-2 production attained upon activation.
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PMID:In vitro analysis of the proliferative potential of T cells from patients with brain tumor: glioma-associated immunosuppression unrelated to intrinsic cellular defect. 140 31

An activation of T-cells that is restricted to the lung has been demonstrated in pulmonary sarcoidosis. The role of blood monocytes (MO) and alveolar macrophages (AM) in this concept of compartmentalized inflammation has not yet been evaluated. In order to elucidate this question, we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by peripheral blood mononuclear cells (PBMNC) and AM in 43 patients with sarcoidosis (32 with active, 11 with inactive disease) without therapy and correlated the spontaneous monokine release to parameters of the T-cell alveolitis and the course of the disease. TNF alpha as well as IL-1 were spontaneously released by AM of the active group, i.e., 2,385 +/- 735 pg/ml/10(8) cells/24 h and 7/12 (IL-1+/total), respectively. Autologous PBMNC were quiescent, releasing only baseline levels of any monokine. AM were not activated in the inactive group, releasing 500 +/- 212 pg/ml/10(6) cells/24 h TNF alpha, whereas 1/5 were IL-1-positive (p less than 0.05 in both comparisons), which is within the range of the control group. Kinetic experiments revealed that the TNF alpha gene of AM is activated in vivo, resulting in TNF alpha mRNA-positive, TNF alpha-releasing cells that, cultured in vitro, regulate the TNF alpha gene transcription down and cease to release TNF alpha. Interestingly, there is no stringent correlation between the spontaneous release of TNF alpha by AM and signs of T-cell activation as soluble interleukin-2 (IL-2) receptor serum concentration, release of IL-2, and expression of IL-2 receptor by alveolar T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis. 173 82

The immunomodulating effect of sizofiran on regional lymph nodes (RLN) was studied in cervical cancer and benign gynecologic tumors comparatively between treated patients (sizofiran intramuscularly (1) 1 day (20 mg) before and (2) 8 days (20 mg) and 1 day (20 mg) before surgery; n = 34) and untreated patients (n = 21). The RLN (internal iliac lymph nodes) were dissected surgically, and freshly obtained mononuclear (MN) cells were studied to observe interleukin-2 (IL-2) production and lymphokine-activated killer cell and natural-killer cell activities. The infiltration of surface phenotype of MN cells into RLN was determined semiquantitatively by immunohistochemistry. Sizofiran augmented IL-2 production of RLN, which was accompanied by a marked increase in the number of cells stained with anti-Leu-3a and IL-2 receptor. This effect was found more often in Stage Ib disease than in Stage 0, and it was not observed in benign tumors. These results suggest that stimulation with some antigens (e.g., cancer antigen in the current study) is necessary to induce immunoaugmentation by sizofiran which has no antigenicity. The augmenting effect was seen even in lymph nodes involved by advanced cervical cancer. Therefore, sizofiran was found to be a potent biologic response modifier in patients with cervical cancer.
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PMID:Augmenting effect of sizofiran on the immunofunction of regional lymph nodes in cervical cancer. 173 19

The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of HLA-DR+ T4 L-BAL, and sIL-2R production is independent of the percentage of IL-2+ L-BAL. Our data indicate that the L-BAL activation markers and the functional activity of T-cells represent independent phenomena.
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PMID:Correlation of clinical and immunologic parameters of the inflammatory activity of pulmonary sarcoidosis. 174 45

An athymic mouse-derived CD4+8+ T-cell clone, N-9F, was established. It expresses both full length gamma and delta T-cell receptor (TcR) mRNA. N-9F clone was not maintained by interleukin-2 (IL-2) alone but required another soluble mediator(s), contained in concanavalin A-stimulated splenocyte culture supernatant, for its proliferation. By culturing N-9F on thymic stromal cells, [3H]thymidine incorporation was retained and expression of IL-2 receptor (IL-2R) was induced. This phenomenon was also observed on thymic stromal cells from H-2 allogeneic mice, but not on other cell types such as splenic adherent cells or fibroblasts. After addition of recombinant IL-2 into the N-9F culture with thymic stromal cells, N-9F showed enhanced IL-2R expression and greatly proliferated. The inability to detect any soluble factors in thymic stromal cell culture supernatant suggests that this interaction is mediated by direct cell contact between T and thymic stromal cells. Because a CD2-negative subclone, N-9.23, also proliferated on thymic stromal cells, there might exist a type of molecule other than CD2/LFA3 or TcR/MHC involved with thymic stroma and T-lymphocyte interaction.
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PMID:Proliferation of an athymic mouse-derived T-cell clone on thymic stromal cells with interleukin-2. 174 73

Trypanosoma cruzi, the causative agent of Chagas' disease, suppresses immune responses during the acute phase and has been shown to induce multiple cellular alterations in activated human T lymphocytes. However, no information is available regarding the effects of this parasite on human B cells. Using an in vitro culture system, in which purified T. cruzi are co-cultured with either peripheral blood mononuclear cells (PBMC) or B-cell-enriched preparations (BCE), we studied whether the organism can induce alterations in DNA synthesis after stimulation with Pansorbin (PS). This response was markedly reduced by the parasite at both suboptimal and optimal PS concentrations, and the extent of the inhibition was augmented as the parasite concentration was increased. Maximal reduction in DNA synthesis was observed when the trypanosomes were incorporated into the cultures at 0 time (i.e. together with PS); the effect was of a much lesser magnitude and undetectable when the parasites were added at 24 and 48 hr, respectively. These results imply that T. cruzi affects a relatively early event during B-cell stimulation. This inference was confirmed by the finding that the proportion of PS-stimulated B cells expressing interleukin-2 (IL-2) receptors was significantly reduced when the parasite was present in the culture. Addition of recombinant human IL-2 did not restore B-cell responsiveness to normal levels. Suppressed B-cell responses were also observed when T. cruzi was separated from the PBMC or the BCE by a cell-impermeable filter, indicating that a soluble factor(s) released by the organism mediated the effect. Accordingly, supernatants of T. cruzi suspensions were found to be suppressive. These results demonstrate for the first time that T. cruzi can affect human B-cell responses and that the mechanism involves inhibition of IL-2 receptor expression.
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PMID:Trypanosoma cruzi induces suppression of DNA synthesis and inhibits expression of interleukin-2 receptors by stimulated human B lymphocytes. 174 80

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.
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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

Ficoll-separated and monocyte-depleted mononuclear cells isolated from normal leukapheresis products were cryopreserved. These cells were incubated with or without 1,000 U/ml of recombinant interleukin-2 (rIL-2) for 4 days, and their lymphokine-activated killer (LAK) and natural killer (NK) activities were measured. IL-2 activation induced a significant increase in the expression of the CD25 antigen. There was no change in CD2, CD3, CD4, CD8, CD16, CD56 and CD57 cell marker expression. Cryopreservation did not induce any change in the membrane antigen expression and in the lymphocyte subsets. The NK activity was well preserved and the decrease of LAK activity of IL-2-activated cells after cryopreservation was not significant. In contrast, cells activated before cryopreservation had a significantly lower cytotoxic activity and the number of cells expressing the IL-2 receptor was also significantly reduced. However, the decrease of CD56 expression was not significant. CD25 expression seemed to be proportional to the LAK activity of the cells. This study demonstrated that cryopreserved lymphocytes, after 4 days of culture with rIL-2, could be as active and could express the CD25 and CD56 cell surface markers in the same manner as fresh LAK cells.
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PMID:The influence of cryopreservation on activity and surface markers of lymphokine-activated killer cells. 176 4

The effect of recombinant interleukin-2 (IL-2) on the proliferation of T-cell depleted leukemic blasts was evaluated in 23 patients with acute myelogenous leukemia (AML). For this purpose, the effect of IL-2 on cell growth, [3H]-thymidine incorporation into the blasts and the expression of IL-2 receptors on cell surface using T-cell depleted blasts were studied. The results showed that IL-2 stimulated [3H]-thymidine incorporation significantly in blasts of 8 out of 23 cases of AML. An IL-2 induced increase in cell number was directly demonstrated in seven out of eight IL-2 responsive patients studied. IL-2 stimulated the proliferation of blasts in monocytic lineage (M4 and M5), but not all M4/M5 leukemics responded to rIL-2. Stimulation of the growth of leukemic cells was not correlated with the expression of Tac antigen on the cell surface, but it was significantly correlated with the expression of IL-2 receptor (IL-2R) beta chain on the cell surface. These results indicate that IL-2 is an active growth factor in certain myeloid leukemia cells, especially of monocytic type.
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PMID:Growth of certain myeloid leukemic cells can be stimulated by interleukin-2. 177 32


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