Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production and targeting of a major T cell derived lymphokine, Interleukin 2 (IL-2), were studied in 23 uremic patients undergoing regular hemodialysis treatment and 20 uremic patients prior to the onset of renal replacement therapy. In hemodialyzed patients, abnormally increased proportions of circulating T cells spontaneously expressing high affinity IL-2 receptors (IL-2 Rec) were detected: they bound a monoclonal antibody specifically directed to the IL-2 Rec 55 kDa chain (Tac antigen) (mean +/- SEM: 7.12 +/- 0.81% in patients vs. 2.15 +/- 0.39% in normal controls, P less than 0.0001) and significantly proliferated in presence of human recombinant IL-2 alone (mean +/- SEM: 5438 +/- 729 cpm in patients vs. 1647 +/- 244 cpm in normal controls). Hemodialyzed patients also exhibited significantly increased serum levels of soluble IL-2 receptor (mean +/- SEM: 4036 +/- 947 U/ml in patients vs. 253 +/- 29 U/ml in normal controls. P less than 0.001). Moreover, a significantly decreased IL-2 activity was detected in the supernatants of stimulated T cells from hemodialyzed patients (mean +/- SEM: 0.93 +/- 0.12 U/ml in patients vs. 2.49 +/- 0.22 U/ml in normal controls, P less than 0.0001). In nine hemodialyzed patients who were analyzed before and immediately after the hemodialysis session no acute modifications of the various parameters analyzed were detected. Although less profound, a similar pattern of T cell abnormalities was observed in the uremic non-hemodialyzed patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo T cell preactivation in chronic uremic hemodialyzed and non-hemodialyzed patients. 268 33

This study investigated the requirements for lymphokines derived by recombinant (rec.) DNA technology for the induction of growth and maturation in highly purified lectin reactive T cell subsets. Nylon purified C57BL/6 lymph node T cells were treated with monoclonal anti-Lyt-2.2 or anti-L3T4 antibodies and fluorescence labeled (FITC) anti-immunoglobulin antibodies and were positively selected into Lyt-2+ (L3T4-) and Lyt-2- (L3T4+) lymphocyte subsets using a fluorescence-activated cell sorter. Sorted T lymphocytes, which were devoid of accessory cells were incubated either in bulk culture (2 X 10(2) - 3 X 10(4) cells/microculture) or under limiting dilution conditions (2.5-1,000 cells/well) with lectin (Concanavalin A, Leukoagglutinin) and rec. human Interleukin 2 (rec. hIL-2) and/or rec. mouse Interferon gamma (rec. mIFN-gamma). The data show that Lyt-2+ lymphocytes respond to lectin and rec. hIL-2 with growth and development of cytolytic activity in the absence of other exogenous factor(s) or accessory cells. The presence of monoclonal antibodies to the Interleukin 2 receptor during the sensitization phase ablated the induction of Con A reactive precursor cells of cytolytic lymphocytes (CTL-P) by either rec. hIL-2 or conventional IL-2 containing lymphokine sources, indicating the essential role of IL-2 during activation of Lyt-2+ T lymphocytes. In contrast, Lyt-2- lymphocytes could not be induced by lectin and rec. hIL-2 alone for proliferation and always required the presence of accessory cells for significant growth. Exogenous rec. m IFN gamma was unable to induce growth and cytolytic activity in Con A reactive Lyt-2+ cells and did not significantly effect their response to rec. hIL-2. Limiting dilution experiments revealed that 10-16% of the Lyt-2+ lymphocytes responded to Con A and rec. hIL-2 with growth (GTL-P). The frequencies of CTL-P, determined under similar conditions, were always lower compared to GTL-P. However the results suggest that the differences observed between both precursor populations is due to differential sensitivity of the detection system rather than to the recruitment of distinct T cell subsets. Furthermore, it was shown that at least 50% of lectin reactive CTL-P were induced by rec. hIL-2 to secrete IFN-gamma under optimal conditions. The finding that some of the conventional lymphokine sources were superior to rec. hIL-2 in the induction of growth and cytolytic activity suggests the existence of mediators distinct from IL-2 that regulate the expansion of CTL-P.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin 2 induces both, growth and maturation of lectin reactive Lyt-2+ but not Lyt-2-precursor cells and regulates the cytolytic potential of effector cells. 308 17

The effect of cyclosporine and metabolite 17 (M17) as well as other CsA-related compounds (CsG, dihydro-CsC, dihydro-CsD, CsH, B5.49, and H7.94) was tested on T lymphocyte clone proliferation. In these experiments, antigen and interleukin 2 (IL-2) dependent long-term T lymphocyte clones derived from a rejected human kidney graft infiltrate were used. They were specifically committed (proliferation and cytotoxicity) for the donor Epstein-Barr virus (EBV)-transformed cells. CsA strongly inhibited clone T cell proliferation induced by the antigen. Inhibition of antigen-driven proliferation was reversed by pure recombinant IL-2 (rec-IL-2) only when low amounts of CsA (less than 25 ng/ml) were used, whereas this lymphokine was ineffective at higher but still pharmacological CsA concentrations (50-500 ng/ml). Increasing rec-IL-2 concentrations did not modify this finding. In addition, CsA, did not inhibit the growth signal(s) induced by rec-IL-2/IL-2 receptor interactions when R-IL-2 is pre-expressed on clone cells. M17 was far less effective in inhibiting antigen-induced clone cell proliferation (50% inhibition at 16 ng/ml versus 500 ng/ml with, respectively, CsA and M17) but was nevertheless inhibitory. This observation, if extended to other metabolites, could be important for interpretation of the relevance of "CsA" concentration through radio-immunoassay monitoring of recipients' blood. Although CsA appeared to display the major inhibitory effect, dihydro-CsC and CsG, as well as B5.49 and H7.94 CsA-related compounds, also exhibited strong activity. Dihydro-CsD was less inhibitory, and CsH had no effect.
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PMID:Effect of cyclosporine, cyclosporine metabolite 17, and other cyclosporine-related compounds on T lymphocyte clones derived from rejected human kidney grafts. I. Inhibition of proliferation. 332 90

In this study the effect of recombinant human interleukin 2 (rec.hIL-2) on the proliferation and maturation of B lymphocytes was investigated. It was found that the presence of rec.hIL 2 results in proliferation of mitogen (LPS)-activated B cell blasts. In addition, it is shown that highly enriched murine B cells can be induced by rec.hIL-2 to proliferate and to develop into antibody-secreting cells (PFC) in the presence of antigen (SRBC). When tested for its effect on B cell preparations enriched for resting (small) or activated (blasted) B lymphocytes, it was found that rec.hIL 2 provides signals for both B cell populations to develop into PFC. In contrast, induction of proliferation by the same lymphokine source was only seen in blasted B cells. The data indicate that IL 2 is involved in the generation of B effector cells by directly acting on their precursors thereby providing differentiation as well as proliferation signals.
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PMID:Recombinant human interleukin 2 directly provides signals for the proliferation and functional maturation of murine B lymphocytes. 387 48

Genetically engineered expression of tumor-specific single chain antibody chimeric receptors (ch-Rec) on human T lymphocytes endow these cells with the parental monoclonal antibody (mAb) dictated tumor specificity and may be useful for clinical immuno-genetherapy. Therefore it was of importance to assess how the densities of tumor-specific receptors and tumor associated antigens (TAA), respectively, affect primary human T lymphocyte functions in relation to target cell susceptibilities to lysis. We therefore studied the functional balance between ch-Rec densities on human T lymphocytes and TAA on tumor cells. The gene construct encoding a ch-Rec derived from (1) a renal carcinoma cell (RCC) specific mouse mAb (G250), and (2) the human signal transducing Fc(epsilon)RI gamma-chain was used. To obtain ch-RecHIGH-POS and ch-RecLOW-POS T lymphocytes, two distinct retroviral vectors were used to introduce the gene constructs into primary human T lymphocytes. Levels of ch-Rec-redirected T lymphocyte mediated tumor cell lysis, as well as lymphokine production were determined using RCC lines as target/stimulator cells, which express either no or increasing densities of the TAA. A functional and dynamic balance between ch-Rec densities on cytotoxic T lymphocytes (CTLs) on the one hand and TAA densities on RCCs on the other, was found. In short, ch-RecHIGH-POS CTLs are triggered by TAAHIGH-POS as well as TAALOW-POS RCCs to lyse tumor cells and produce (IFN-gamma and TNF-alpha) lymphokine. In contrast, ch-RecLOW-POS T lymphocytes are only triggered for cytolysis and lymphokine production by relatively TAAHIGH-POS RCCs. In conclusion, (1) the activation of T lymphocyte responses is co-determined by the expression levels of the ch-Rec on T lymphocytes and the TAA on tumor cells and (2) at relatively high T lymphocyte ch-Rec expression levels the CTLs lyse tumor cells with a wide range of TAA densities. Gene Therapy (2000) 7, 35-42.
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PMID:Functional balance between T cell chimeric receptor density and tumor associated antigen density: CTL mediated cytolysis and lymphokine production. 1068 14