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)

The inhibitory effects of CsA in cell-mediated immunity are well known. There is controversy about whether CsA directly inhibits the function of accessory cells as well as T lymphocytes. We have used northern blotting to compare the effects of CsA on several human monocyte and T cell mRNAs, and we have performed "CsA-pulsing" experiments to separately evaluate the effect of the drug on accessory and T cells during lymphocyte mitogenesis. CsA blocked the induction of several lymphokine mRNAs in stimulated T cells including IL-2, IFN-gamma, and IL-4. CsF, an analog that is ten times less active than CsA as an immunosuppressant, was some ten times less active in inhibiting lymphokine gene expression in culture. CsA and CsF had little effect on the mRNA for the 55 KD low-affinity IL-2 receptor, but there was decreased expression of the TAC antigen. Exogenous IL-2 reversed the CsA-mediated suppression of cell proliferation and TAC expression. This indicates that the primary block with cyclosporines is at the level of lymphokines rather than lymphokine receptors. CsA did not reduce the levels of several monocyte mRNAs, however. These included c-myc and Il-1 alpha/beta mRNAs, induced by PMA plus Con A, as well as HLA-DR alpha and gamma-Ip10 mRNAs in monocytes treated with IFN-gamma. When monocytes were pulsed with CsA, there was no reduction in their subsequent accessory function for anti-CD3 and lectin responses. T lymphoblasts pulsed with CsA, however, did not proliferate or release growth factor. Likewise in the primary MLR between dendritic cells and T cells, dendritic cells were not impaired following pulsing with CsA, whereas treated T cells made 70% less IL-2. The primary site of action of CsA therefore seems to be the production of lymphokines by T lymphocytes.
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PMID:Evidence that cyclosporine inhibits cell-mediated immunity primarily at the level of the T lymphocyte rather than the accessory cell. 313 67

We studied the effect of highly purified recombinant interleukin 2 from Escherichia coli (rIL-2) on antibody production by our human hybridomas. Increasing concentrations of rIL-2 were directly related to increased production of immunoglobulin, which reached peak levels of 13-25 micrograms/ml, a 10- to 20-fold increase over untreated hybridomas. We were unable to demonstrate large quantities of the IL-2 receptor on the hybridomas as measured by an anti-TAC monoclonal antibody. The data suggest that the antibody enhancement phenomenon is mediated by IL-2 and that is a new, effective way to achieve higher levels of immunoglobulin from human hybridomas.
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PMID:Recombinant human interleukin 2 (rIL-2) enhancement of antibody production by human-human hybridomas. 313 33

Triggering of the T-cell receptor by anti-CD3 monoclonal antibodies (mAb), for example OKT3, induces accessory cell (AC)-dependent interleukin-2 (IL-2) and IL-2 receptor synthesis, and ultimately, T-cell proliferation. We report on the ability of a HLA-class I specific monomorphic mAb, namely FMC16, to inhibit OKT3-driven T-cell mitogenesis. FMC16 was apparently selective for OKT3 because it did not block Concanavalin A (Con A) or mAb Leu-4 induced proliferation. Moreover, this effect was not due to non-specific toxicity nor interference with OKT3 binding. Kinetic analysis showed that FMC16 was inhibitory when added up to 24 hr after initiation of culture. FMC16 drastically reduced both IL-2 production and IL-2 receptor expression, but did not interfere with IL-2 responsiveness. The inhibitory effects were not altered by the addition of exogenous IL-2 if FMC16 was present at the beginning of culture; however, IL-2 did restore proliferation if FMC16 was not added until 3 to 6 hr after initiation of culture. This coincided exactly with an IL-2 mediated increase in the level of TAC-positive cells. Furthermore, T-cell activation triggered by the synergistic action of OKT3 and a phorbol ester (TPA) in the absence of AC was also blocked by FMC16, suggesting that inhibition was not AC-dependent. Taken together, these results indicate that FMC16 interferes with early signals leading to IL-2 production and IL-2 receptor expression and suggest that HLA-class I determinants play an early role in T-cell activation.
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PMID:Specific inhibition of OKT3-driven T-cell mitogenesis by an anti HLA-class I monoclonal antibody. 326 8

Interleukin-2 (IL-2) has been shown to inhibit oligodendrocyte progenitor cell proliferation. Within the immune system, IL-2 biological action is dependent strictly on the expression of the IL-2 receptor. The antibody TAC, which specifically binds the lymphocyte IL-2 receptor, has been shown to also bind oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium. The expression of the TAC antigen was found necessary for IL-2 inhibition of oligodendrocyte progenitor cell proliferation. After IL-2 induced down-regulation of the TAC antigen, the progenitor cell was unresponsive to IL-2, even 72 hr after IL-2 withdrawal. During this unresponsive period, the oligodendrocyte progenitor cell was immunocytochemically negative for the TAC antigen. Thus, in contrast to IL-2 receptors on T-cells, IL-2 does not up-regulate its receptor on oligodendrocyte progenitor cells. However, upon interleukin 1 (IL-1) addition both IL-2 responsiveness and TAC immunocytochemical staining reappeared. These data suggest that IL-2 inhibition of progenitor cell proliferation depends on the expression of the TAC antigen, which can be regulated by IL-1.
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PMID:Interleukin-2 inhibition of oligodendrocyte progenitor cell proliferation depends on expression of the TAC receptor. 350 Mar 22

Peripheral blood (PBL) and synovial fluid lymphocytes (SFL) from 18 patients with definite rheumatoid arthritis (RA) and from one patient with Reiter's disease (RD) were examined for their capacity to absorb quantitatively interleukin-2 (IL-2) from a standardized, lectin-free IL-2 source. For comparison normal ConA blasts and PBL from various inflammatory and noninflammatory diseases as well as from healthy control persons were studied. IL-2 activity was quantitated by measuring 3H-thymidine-2-deoxyriboside uptake in the IL-2 dependent murine T cell line CTL6. ConA blasts exhibited a high IL-2 absorption capacity and served as a positive control for calibrating the absorption assay. In a population of normal PBL at least 5-10% of ConA blasts were required to detect IL-2 absorption. Significant absorption was assumed if more than 50% of IL-2 activity was removed from 200 microliters of a lectin-free IL-2 standard following incubation with 5 X 10(6) lymphoid cells for 2 h at 4 degrees C; this criterion was fulfilled with 8 out of 20 SFL and 4 out of 14 PBL preparations from RA patients. As a rule SFL absorbed more IL-2 than PBL. Control PBL did not absorb significant quantities of IL-2. PBL from the RD patient apparently produced an IL-2 inhibitor during incubation with the IL-2 standard. IL-2 absorption by ConA blasts and SFL was fully inhibited by preincubation of the absorbing cells with monoclonal anti-TAC antibody, a reagent known to react with the human IL-2 receptor. The results are discussed in view of current concepts of antigen/mitogen induced T cell activation.
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PMID:Quantitative absorption of interleukin-2 by peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. 392 39

The analysis of the expression of the alpha chain of the IL-2 receptor (CD25, TAC) on the surface of B lineage cells in mouse bone marrow reveals that it is a useful marker to distinguish pre-B-I from pre-B-II cells. CD25 is not expressed on CD45R(B220)+ c-kit+ CD43+ TdT+ lambda 5+ c mu- sIg-IgH chain locus DJH-rearranged pre-B-I cells of mouse bone marrow. It is expressed on large cycling CD45R(B220)+ c-kit- CD43+ TdT- lambda 5+ c mu+ sIg- and on small resting CD45R(B220)+ c-kit- CD43- TdT- lambda 5- c mu- sIg- IgH chain locus VHDJH-rearranged pre-B-II cells. Therefore, the transition from pre-B-I to large pre-B-II cells is marked by the downregulation of c-kit and terminal deoxynucleotidyl transferase (TdT), and by the upregulation of CD25. SCID, RAG-2T, microMT and lambda 5T mutant mice do have normal, if not elevated numbers of pre-B-I cells but lack all CD25+ pre-B-II cells in their bone marrow. The expression of a transgenic H chain under control of the microH chain enhancer in RAG-2T bone marrow B lineage precursors allows the development of large and small CD25+ pre-B-II cells. The results suggest that the differentiation of pre-B-I to pre-B-II cells in mouse bone marrow requires the expression of microH chains and surrogate L chains in membranes, probably on the surface of precursor B cells.
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PMID:IL-2 receptor alpha chain (CD25, TAC) expression defines a crucial stage in pre-B cell development. 752 94

Renal biopsies were performed 1 week following renal transplantation at a time without clinical evidence of rejection in 43 patients (13 females, mean age 48 years range 18-60 and 30 males, mean age 43 years range 17-59 years). Thirty-six biopsies were available for histological or immunohistochemical analysis. Immunohistochemical analyses were performed with monoclonal antibodies against leukocytes (CD45), monocytes (WT14), complement factor 3 (C3), T-cells (Leu4), T-cell receptor alpha beta and gamma delta, tumour necrosis factor alpha (TNF alpha), IL-2 receptor (IL2-R, TAC), intercellular adhesion molecule-1 (ICAM1) and HLA-DR. The slides were scored semiquantitatively with the observers having no knowledge of clinical or patient data. TNF alpha and IL-2R were also measured by quantative PCR. None of the studied parameters correlated to delayed graft function or graft loss. Histological analysis showed that both focal interstitial infiltrate (18/35) and tubular basement membrane disruption (11/35) were followed by a higher incidence of subsequent rejection (P = 0.03 and 0.02 respectively). Also positivity for WT14 around tubuli (P = 0.02) was associated with subsequent occurrence of rejection. The intensity of staining of ICAM-1 on PTC as well as TAC on proximal tubular cells was associated with the number of subsequent rejection episodes. The association between the IL-2 receptor and subsequent rejection was also found applying PCR to the tissue specimens. We conclude that the presence of focal interstitial infiltrates and tubulitis in 1-week biopsies from well-functioning grafts carries an increased risk of subsequent rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation by histology, immunohistology and PCR of protocollized renal biopsies 1 week post-transplant in relation to subsequent rejection episodes. 756 15

Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) in 14 patients with anorexia nervosa (AN) was significantly lower than in 14 age-matched healthy controls. Follow-up samples in four patients displayed low levels, except in two when they recovered the IFN-gamma production as the hormonal cycles were restored. A large interindividual variation for the lymphocyte proliferative response was observed in 30 AN patients. DNA synthesis of PBMC was normal in 8 patients (27%), significantly increased in 6 (20%) (P < 0.001), and significantly decreased in 16 (53%) (P < 0.001). IFN-gamma inhibition was reversed by culturing a control lymphocyte population with monocytes from patients with AN. This was not observed in cultures of control monocytes and AN lymphocytes. IL-2 receptor (TAC subunit) was assessed and no difference was found in the number of TAC-positive cells between patients and controls. These results point out impaired production of the immunomodulator cytokine IFN-gamma as a major functional defect of AN peripheral lymphocytes.
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PMID:Low lymphocyte interferon-gamma production and variable proliferative response in anorexia nervosa patients. 828 28


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