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)

Rats were immunized systemically with sheep red blood cells (SRBC) and treated with either FK-506 (1 mg/kg/day) or cyclosporin A (CsA) (25 mg/kg/day) for 7 days. Profound (greater than 90%) suppression of the production of splenic IgM-secreting plasma cells and circulating antibody levels was observed in animals receiving either drug. Immunosuppression was accompanied by significant increases in the incidence and absolute numbers of OX8+ (T-cytotoxic/suppressor) lymphocytes in the spleen, and there were corresponding reductions in the W3/25+:OX8 (CD4+:CD8+) ratio. The magnitude of these changes was not affected by drug combination. There were no significant alterations in B cells with either agent, whilst a small but significant increase in the incidence of macrophages was observed in all drug-treated groups. Neither FK-506 nor CsA affected IL-2 receptor (OX39) or MHC class II (OX6) antigen expression. This study demonstrates the remarkable immunosuppressive potency of FK-506 and its underlying capacity, like CsA, to affect regulatory T-lymphocyte subsets in vivo.
Immunology 1988 Sep
PMID:Spleen lymphocyte populations and expression of activation markers in rats treated with the potent new immunosuppressive agent FK-506. 246 Apr 1

The activation of resting T cells to interleukin 2 (IL-2) production and DNA synthesis via Ti-CD3 is dependent on accessory cells (AC). Using positively selected, resting T cells activated with particle-bound anti-CD3, we investigated the ability of various cell lines to function as AC. We found that cell lines able to act as AC all expressed LFA-3, while cell lines not expressing LFA-3 were unable to provide AC signals. This applied to CD3+, CD4+, and CD8+ T cells. Sheep red blood cells (SRBC), which express LFA-3-like molecules, also had a weak, but significant AC function in this test system. Both CD4+ and CD8+ T cells activated with particle-bound anti-CD3 could be induced to enter DNA synthesis in the absence of AC when monoclonal antibodies reacting with CD2 were present instead of AC. IL-2 production could be detected in the latter cultures but not when positively selected CD3+ or CD2+ T cells were cultured alone. Our data suggest that activation of resting T cells via CD3 will lead to IL-2 receptor expression, while the interactions between LFA-3 and its ligand CD2 provide the necessary secondary signals for IL-2 production and induction of DNA synthesis.
Scand J Immunol 1988 Sep
PMID:Accessory cell-dependent T-cell activation via Ti-CD3. Involvement of CD2-LFA-3 interactions. 246 80

Clinical use of the antitumor antibiotic bleomycin (BLM) is associated with the development of interstitial pulmonary fibrosis. Shortly after acute lung damage caused by intratracheal (it) administration of BLM to experimental animals there is an influx of inflammatory cells which are believed to modulate the process of fibrosis. This study was undertaken to determine what subpopulations of lymphocytes were in the bronchoalveolar lavage (BAL) cell population of C57BL/6J mice at various times after a single it dose of BLM and to determine whether BAL T-lymphocytes were activated after BLM treatment. The BAL lymphocyte population was analyzed by differential cell analysis and flow cytometry utilizing monoclonal antibodies specific for lymphocyte subpopulations. The majority of lymphocytes in the BAL of control and BLM-treated mice were T-lymphocytes, with less than 10% being B-cells. During the first 7 days after BLM the number of Lyt-2+ T-cells exceeded L3T4+ T-cells while in control mice the reverse was observed. The percentage of BAL lymphocytes expressing the IL-2 receptor did not change significantly at 3 and 7 days after BLM treatment, but was significantly decreased at Day 14. In contrast, the total number of lymphocytes expressing the IL-2 receptor was increased at all time points investigated. These results demonstrated that the majority of lymphocytes in the BAL were T-cells and that while the percentage of activated lymphocytes did not increase following BLM treatment, the absolute number did and this increased number of activated lymphocytes may be important in the disease process.
Toxicol Appl Pharmacol 1989 Sep 15
PMID:Alteration of bronchoalveolar lavage cell populations following bleomycin treatment in mice. 247 69

By interaction with monocytes, interleukin-2 (IL-2) suppressed natural killer (NK) cell cytotoxicity (NKCC) of human, Percoll-fractionated, low-density mononuclear cells. The NK-suppressive effect of IL-2 was independent of de novo formation of prostaglandins or protein since it was unaffected by treatment with indomethacin and cycloheximide, respectively. A monoclonal antibody to the p55 (beta) moiety of the IL-2 receptor (anti-Tac/anti-CD25) blocked IL-2-induced NKCC suppression but did not affect the NK-enhancing effect of the lymphokine. We conclude that IL-2 exerts a monocyte-dependent, IL-2 beta-receptor mediated suppressive influence on human NK cells.
Clin Exp Immunol 1989 Sep
PMID:Interleukin-2 can induce suppression of human natural killer cell cytotoxicity. 250 16

Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.
Nihon Ketsueki Gakkai Zasshi 1989 Sep
PMID:CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells. 251 16

Epstein-Barr virus (EBV) readily immortalizes human peripheral blood lymphocytes (PBL) in vitro. However, during the past several years, we found that PBL from two exceptional EBV-seropositive healthy adult individuals were refractory to immortalization by EBV. We report here a study aimed at learning about the immunobiological features which differentiate these EBV-resistant (R) PBL from others which are susceptible (S) to EBV immortalization. Results of this investigation indicate that: (a) Following EBV infection, R-PBL produced significantly higher amounts of interferon gamma (IFN-gamma) than S-PBL. There were however no differences in regard to interferon alpha production between these two types (R and S) of EBV-infected cultures. (b) R-PBL had a maximal interleukin-2 (IL-2) production by S-PBL occurred at least 48 hr later, i.e., at Day 7. (c) The percentage of non-B cells expressing the IL-2 receptor was also higher in EBV-infected R-PBL than S-PBL. (d) In contrast, expression of IL-2 receptors after EBV infection was higher on B cells from S-PBL than on B cells from R-PBL. Interestingly, no differences were noted in regard to IL-2 receptor expression between R-PBL and S-PBL treated with mitogens (i.e., phytohemagglutinin and pokeweed mitogen). (e) Finally, using anti-IL-2 and anti-IFN-gamma antibodies in EBV-infected R-PBL cultures, we were able to obtain EBV-induced immortalization of these cultures. Taken together, these results suggest that an early IL-2 synthesis and high IFN-gamma production by EBV-infected PBL play an important role against lymphocyte immortalization by EBV.
Cell Immunol 1989 Sep
PMID:Differential interleukin-2 and interferon-gamma production by human lymphocyte cultures exceptionally resistant to Epstein-Barr virus immortalization. 254 40

The leukocyte-common antigen (L-CA) is a family of large molecular weight glycoproteins uniquely expressed on the surface of all nucleated cells of hematopoietic origin. The glycoprotein consists of a heavily glycosylated exterior domain, a single membrane spanning region, and a large cytoplasmic domain that contains tyrosine phosphatase activity. To investigate the function of this family, we generated T cell clones that lacked L-CA (L-CA-). The expression of the alpha beta T cell receptor, CD3, CD4, IL-2 receptor (p55), LFA-1, Thy-1, and Pgp-1 (CD44) was normal. The L-CA- T cell clones failed to proliferate in response to antigen or cross-linked CD3; however, they could still proliferate in response to IL-2. An L-CA+ revertant was obtained and the ability to proliferate in response to antigen and cross-linked CD3 was restored. These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen.
Cell 1989 Sep 22
PMID:Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. 255 Jan 43

Human peripheral blood T cells were stimulated to proliferate when cultured with submitogenic doses of PMA and goat antibodies to 5'-nucleotidase (5'-NT). The degree of proliferation, as measured by [3H]TdR incorporation on day 3, was similar to that achieved by stimulation with PHA. Anti-5'-NT antibodies had no effect on PHA-induced proliferation. Maximal stimulation was achieved with 0.6 to 1.0 ng/ml of PMA and 125 micrograms/ml of IgG isolated from a goat anti-5'-NT antiserum. Both intact IgG and F(ab')2 fragments were stimulatory. IL-2R expression and IL-2 secretion were also induced by anti-5'-NT antibodies and PMA. Anti-5'-NT-induced proliferation was inhibited greater than 95% by a murine anti-IL-2 receptor mAb and required less than 0.3% monocytes. Similar results have been obtained with a murine mAb specific for 5'-NT. As expected, anti-5'-NT antibodies and PMA did not induce the proliferation of ecto-5'-NT-T cells isolated by cell sorting. Pretreatment of total T cells with phosphatidylinositol-specific phospholipase C removed an average of 89% of the 5'-NT activity from the cell surface and also inhibited by 83% the ability of the cells to proliferate in response to anti-5'-NT antibodies and PMA. Thus, the activation signal provided by anti-5'-NT antibodies is apparently transduced, in large part, by a form of the enzyme that is attached to the membrane via glycosyl-phosphatidylinositol linkage. These data suggest that 5'-NT may play a role in lymphocyte activation as has been proposed for other glycosyl-phosphatidylinositol-anchored lymphocyte surface proteins.
J Immunol 1989 Sep 15
PMID:Antibodies to 5'-nucleotidase (CD73), a glycosyl-phosphatidylinositol-anchored protein, cause human peripheral blood T cells to proliferate. 255 May 43

Periodic assay of IL-2 receptor expression on the surfaces of peripheral blood lymphocytes might provide information predictive of in vivo immunologic events. This study compares two methods of determining IL-2 receptor expression after renal transplantation in cynomolgus monkeys. The first utilized single color staining of peripheral blood mononuclear cells with mouse anti-human IL-2 receptor monoclonal antibody followed by a fluorescein-labeled goat anti-mouse IgG antibody. Epics C cell sorter windows were set to count cells of the size and granularity of normal lymphocytes. The second utilized two-color staining with fluorescein-labeled anti-IL-2 receptor antibody, combined with phycoerythrin-labeled anti-CD4 antibody or with phycoerythrin-labeled anti-CD8 antibody. Two-color staining allowed the sorter windows to be enlarged to count all mononuclear cells, regardless of size or granularity, without introducing the contaminating effects of monocytes. Data obtained from single-color staining showed no consistent or significant expression of the IL-2 receptor on peripheral lymphocytes in association with the rejection process. Data obtained from two-color staining revealed an increase of IL-2 receptor expression on peripheral T cells of at least 10% from the postoperative baseline, which preceded the creatinine rise from allograft rejection in 13 of 13 animals. Increases in IL-2 receptor expression on T cells were not specific to rejection, however. Some animals in which treatment produced a delay of rejection showed a transient rise in IL-2 receptor expression around post-transplant day 5, which was not followed by a rise in creatinine. The two-color staining technique described provides a sensitive means of detecting IL-2 receptor expression in vivo and documents the association of increases in IL-2 receptor expression on T cells with rejection.
Transplantation 1989 Sep
PMID:Interleukin 2 receptor expression on peripheral blood lymphocytes in association with renal allograft rejection. 257 Dec 2

Patients were entered into a randomized trial of prophylaxis for renal allograft rejection by the administration of an anti-human IL-2 receptor antibody, anti-Tac, during the first ten days posttransplant. Interleukin-2 receptor (IL-2 R) expression was measured using two anti-IL-2 R monoclonal antibodies (moAbs), anti-Tac and 1HT4-4H3. These two antibodies recognize closely spaced epitopes on the 55 kD chain of the IL-2 R. IL-2 R expression was examined on peripheral blood small lymphocytes in three groups of patients who received: (A) cyclosporine CsA and prednisone for baseline immunosuppression (n = 9); (B) anti-Tac with CsA and prednisone as baseline immunosuppression (n = 12); and (C) anti-Tac with azathioprine and prednisone as baseline immunosuppression (n = 5). We found that large numbers of T cells express IL-2 receptors despite the presence of anti-Tac (average of IL-2 R-positive cells at day of peak IL-2 R expression 56.0 +/- 20.8% in group A, 65.2 +/- 26.6% in group B, 21.0 +/- 7.4% in group C). IL-2 R expression did not correlate with clinical activity, and the presence or accessibility of epitopes on the same 55 kD chain varied dramatically from patient to patient.
Transplantation 1989 Sep
PMID:Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody. 257 Dec 3


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