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 requirements for maintenance of allospecific CD8+ Ts cells generated in the rat primary MLR were investigated. Allospecific CD8+ Ts cells rapidly lose their activity over 72 hr in secondary culture with media alone, whereas low concentrations of rIL-2 (less than 1 U/ml) are able to maintain potent CD8+ Ts cell activity. This Ts cell activity is maintained at rIL-2 concentrations which do not result in significant cell proliferation. Therefore, cell proliferation per se is not a requirement to maintain Ts cell activity, although the CD8+ Ts cells can proliferate to rIL2 in a concentration-dependent manner. An anti-IL-2 receptor monoclonal antibody significantly inhibited the maintenance of Ts cell activity. Two-color flow cytometric analysis demonstrated that Ts cells cultured in rIL-2 maintain upregulation of their high-affinity IL-2 receptor. Although allospecific Ts cells maintained in secondary culture with rIL-2 for 48 hr maintained antigen specificity, there is also the induction of an antigen-nonspecific population. After 168 hr in secondary culture the Ts cells have lost allospecificity, although Ts activity can be maintained with rIL2 in continuous culture for up to 4 weeks.
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PMID:Suppressor cells and T cell synergy in the primary MLR: interleukin-2 is required for the maintenance of rat CD8+ suppressor cells. 170 2

In addition to the regulation of B lymphocyte growth and differentiation, the cytokine IL-4 (BSF-1) exerts effects on T lymphocytes and other bone marrow-derived lineages. We show here that recombinant mouse IL-4 synergizes with low levels of IL-2 to increase the yield of cytotoxic activity in a primary MLR, and the proliferation of both cloned IL-2-dependent CTL lines and cells obtained from a primary MLR. IL-4 did not induce the proliferation of any of several cloned CTL cell lines on its own. It also did not replace IL-2 in stimulating the growth or reactivation of quiescent, antigen-dependent CTL clones. However, IL-4 was synergistic with IL-2 after reactivation of the quiescent cells with antigen plus IL-2. Enhancement by IL-4 of the IL-2-driven proliferation of an antigen-independent line was blocked by the addition of anti-IL-4 monoclonal antibody. Although incubation of the CTL clones with IL-4 or with IL-2 plus IL-4 induced a transient increase in the expression of the mRNA encoding the 55 kDa IL-2 receptor, no change in the number or affinity of IL-2 receptors because of IL-4 was detected. This suggests that IL-4 does not potentiate the IL-2 response by altering IL-2 receptor levels. Instead, we propose that the synergistic effect of IL-4 is mediated by a different signalling mechanism from that used by IL-2.
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PMID:IL-4 potentiates the IL-2-dependent proliferation of mouse cytotoxic T cells. 213 90

The effect of FK506 on in vitro human lymphocyte responses was assessed in comparison with cyclosporine. FK506 suppressed, in a dose-dependent fashion, the lymphocyte response to stimulation with PHA and with alloantigens in primary mixed lymphocyte reactions at a 70-100-fold lower concentration than CsA--namely, 50% inhibition (IC50) was obtained with 8.6 nM FK506 and with 750 nM CsA in the PHA response, and with 0.21 nM FK506 and with 20 nM CsA in MLR. Allocytolytic T lymphocyte induction was also inhibited by FK506, whereas the ability of CTL to lyse targets was not affected by the agent, indicating that FK506 did not affect the recognition and binding of alloantigen by CTL. FK506 inhibited, in a dose-dependent fashion, both IL-2 receptor and transferrin receptor expression on the alloactivated lymphocytes--whereas this agent inhibited only incompletely both expression of both receptors on lymphocytes stimulated with PHA. Lymphocytes from primary MLR cultured in the presence of FK506 were tested for suppressor cell activity on day 8 of culture. FK506 did not allow for the expression of alloantigen-activated suppressor cells when used in a dose sufficient to inhibit CTL generation.
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PMID:Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. I. Inhibition of expression of alloantigen-activated suppressor cells, as well as induction of alloreactivity. 246 92

Functionally distinct subpopulations within the CD4+ subset of T lymphocytes have been described in man, rat, and mouse. In the rat different functions have been assigned to CD45R+ and CD45R- T helper cells. The CD45R+ in contrast to the CD45R- T helper cells have been reported to produce IL-2 and to proliferate well in response both to Con A and in MLR. In the present investigation the kinetics of the response to Con A by the CD45R+ and CD45R- rat T helper subsets have been analyzed. We confirm a strong proliferative response to Con A by CD4+CD45R+ rat T lymphocytes and also that they are the best IL-2 producers. We further demonstrate that CD4+CD45R- cells also produce IL-2, although in order to appreciate this production quantitatively by assays of the culture supernatants it was necessary to block IL-2 absorption by IL-2 receptor (IL-2R) antibodies. This blockage was of importance also in comparisons of the two subsets, since they showed different kinetics of IL-2R appearance. It is demonstrated that the CD4+CD45R- cells respond more rapidly to Con A than the CD4+CD45R+ cells as reflected by phenotypic conversion, IL-2 production, and proliferation. The fast response of the CD4+CD45R- T subset shown in the present study of rat cells and analogous studies of human cells suggests that the memory compartment of T cells besides other characteristics also has the capacity for a more rapid response than naive lymphocytes.
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PMID:Rapid response to Con A by CD4+CD45R- rat memory lymphocytes as compared to CD4+CD45R+ lymphocytes. 252 20

To assess the role of decidual cells (DC) in the maintenance of pregnancy, immunosuppressive activity of culture supernatants from human DC were investigated. Dispersed DC suspensions from decidual tissue of early pregnancies were prepared by an enzyme digestion method using collagenase and DNase, and were enriched over 90 per cent without contamination of macrophages and lymphocytes in the fraction, with specific gravity between 1.033 and 1.044 (fraction 2 [Fr2] ) by a Percoll discontinuous density gradient method. The culture supernatants of Fr2 cells suppressed the responses of normal peripheral blood lymphocytes to PHA, MLR, and killer T cell generation at the 50 per cent concentration. To determine the mechanism of the immunosuppressive activity of the culture supernatants, the effect of the supernatants on interleukin-2 and gamma-interferon production, as well as IL-2 receptor expression, on PBL was investigated. The supernatants from 3 x 10(6)/ml of DC cells inhibited not only IL-2 and gamma-INF production, but also IL-2 receptor expression, compared with normal controls. The supernatants also suppressed immunoglobulin (IgG and IgM) production by pokeweed mitogen-stimulated B cells. To purify the suppressor factor from culture supernatants of DC, serum free culture supernatants of 3 x 10(6)/ml of DC, which showed 32 per cent of inhibitory activity on MLR, were applied to gel filtration. Fractions between mw 67,000 and 43,000 suppressed the MLR. These results suggest that DC from decidua of early pregnancy excrete an immunosuppressive factor with a molecular weight between 43,000 and 67,000 daltons.
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PMID:Characterization and analysis of soluble suppressor factor from early human decidual cells. 252 5

Esculetin (6,7-dihydroxycoumarin) was found to inhibit dose-dependently the proliferation of human T cells stimulated by PHA or phorbolester plus ionomycin. Proliferation in autologous and allogeneic MLR and generation of cytotoxic T cells under limiting dilution conditions were also suppressed, with more than 90% inhibition seen at 50 microM esculetin. The immunosuppressive effect of esculetin was not due to toxicity. Esculetin did not inhibit interleukin-2 (IL-2) production, nor did it interfere with the appearance of IL-2 receptors on stimulated T cells, as judged by immunofluorescence using anti-Tac monoclonal antibody. These results show that esculetin inhibits T-cell activation at a site distal to production of IL-2 and IL-2 receptor expression.
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PMID:Esculetin inhibits T cell activation without suppressing IL-2 production or IL-2 receptor expression. 265 16

Fresh lymph-borne (veiled) dendritic cells (L-DC) in the rat are almost totally negative for the interleukin-2 (IL-2) receptor detected by the monoclonal antibody (mAb) MRC OX39. After 16 hr culture more than 90% of L-DC are OX39 positive, and increased levels of expression can be seen within 5 hr culture. In cultures of L-DC and allogeneic lymphocytes. L-DC appear to express the IL-2 receptor more rapidly than lymphocytes. The intensity of labelling of L-DC is variable but maximal levels are similar to those seen on lymphoblasts. Culture in the presence of concanavalin A (Con A)-stimulated spleen cell supernatants or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) results in a more rapid and intense expression of the IL-2 receptor by L-DC. L-DC cultured following rigorous T-cell depletion, or derived from athymic rats also express the IL-2 receptor after culture with GM-CSF. Cultured, but not fresh, L-DC bind iodinated recombinant IL-2 in a dose-dependent manner and binding is inhibited by excess unlabelled ligand. The amount of IL-2 bound varies but maximal amounts are similar to those bound by lymphoblasts. Following intravenous endotoxin injection, a large proportion of freshly collected L-DC express the IL-2 receptor and the number of L-DC released into the lymph is increased. An antibody to the IL-2 receptor which blocks an allogeneic MLR has no effect on a xenogeneic MLR using rat L-DC as stimulators and mouse lymphocytes as responders.
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PMID:Properties of lymph-borne (veiled) dendritic cells in culture. II. Expression of the IL-2 receptor: role of GM-CSF. 268 Sep 7

An immunosuppressive factor was obtained from culture supernatants of early human decidual cells. The suppressor factor was concentrated by gel filtration in a fraction with a molecular weight between 43,000 and 67,000 daltons. It was further purified by biochemical methods. Four peaks were obtained in the fraction with molecular weight between 43,000 and 67,000 daltons by anion exchange chromatography. Only the second peak had immunosuppressive activity in MLR. Lentil-lectin affinity chromatography of this suppressor factor showed that the suppressor factor had no affinity for lentil-lectin sepharose. Isoelectric focusing of the suppressor factor demonstrated four bands. The protein isoelectric (PI) point was approximately 7.50 in one band and between 6.85 and 7.35 in the other three bands. These results demonstrate that the suppressor factor is not glycoprotein but protein, whose PI is between 6.85 and 7.50. The suppressive effect of this purified factor on lymphokine production and lymphocyte activation was investigated. The addition of the purified suppressor factor to a culture of PBL stimulated with PHA suppressed not only IL-2 production and gamma-INF production, but also BSF-2 production. IL-2 receptor expression and transferrin receptor expression of PBL stimulated with PHA were also suppressed by addition of the suppressor factor. These results demonstrate that this suppressor factor inhibits lymphokine production and lymphocyte activation.
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PMID:Immunochemical characterization of the suppressor factor from early human decidual cells. 279 18

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 have earlier shown that first trimester human decidual cells (typical decidual cells and decidual macrophages) suppress lymphocyte alloreactivity (MLR and CTL generation) in vitro in an MHC-unrestricted manner and that this suppression is mediated by PGE2. The present study explored the mechanisms underlying this suppression by noting the effects of decidual cells (+/- indomethacin or anti-PGE2 antibody) or chemically pure PGE2 on numerous T lymphocyte activation events following allogeneic stimulation in mixed lymphocyte culture (MLC) or polyclonal activation with Con A. The results revealed that this suppression was the net result of an action of PGE2 on at least two events during lymphocyte activation: (i) a down-regulation of IL-2 receptor development on lymphocytes, quantitated with a radioimmunoassay and radioautography; this was noted in MLC or Con A-stimulated lymphocyte cultures in the presence of decidual cells (reversible in the presence of indomethacin or anti-PGE2 antibody), or PGE2, but not PGF2 alpha; (ii) an inhibition of IL-2 production in the MLC, measured with a bioassay using an IL-2-dependent T cell line (CTLL-2) and a recombinant IL-2 standard. These effects blocked cell proliferation and eventual generation of killer cells in the MLC. Decidual cells or PGE2 did not interfere with IL-2-dependent proliferation of CTLL-2 cells, which require an interaction between IL-2 receptors on these cells and IL-2. Finally, neither agent interfered with the lytic function of CTL, once generated. These results indicate that the PGE2-mediated immunosuppressor function of early gestational human decidual cells is accomplished by an afferent blockade of the early events in T lymphocyte activation.
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PMID:Suppression of lymphocyte alloreactivity by early gestational human decidua. II. Characterization of the suppressor mechanisms. 326 15


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