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

We studied the effect of rat rec-IFN-gamma, human rec-IL-2, and an IgG1 monoclonal antibody (DB1) directed against rat IFN-gamma on allograft survival in the rat in various experimental conditions. The DB1 monoclonal antibody did not prolong heart allograft survival in the (LEW/BN)F1 to LEW combination, even when used at high doses (2 mg/rat x 9 days). Rec-IFN-gamma induced major histocompatibility antigen expression in vivo, but its administration had no effect on the graft survival either of untreated LEW recipients of (LEW x BN)F1 heart allografts or of donor blood-transfused LEW recipients. In addition, rec-IFN-gamma alone had no effect on graft survival in cyclosporine-treated rats. In contrast, rec-IL-2 shortened heart allograft survival both in untreated and in cyclosporine-treated recipients. Rec-IFN-gamma partially reversed the effects of rec-IL-2 in cyclosporine-treated rats. The data suggest that in vivo administration of IFN-gamma in allograft recipients may have a suppressor effect, in addition to the postulated augmenting effect on the immune response by increasing MHC antigen expression.
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PMID:Effect of recombinant interferon gamma and interleukin-2 and of a monoclonal antibody against interferon gamma on the rat immune response against heart allografts. 190 47

The effects of a partially purified, splenocyte-derived murine interferon (MuIFN-gamma N) and a recombinant IFN-gamma (MuIFN-gamma R) on the T suppressor pathway and on the T effector cells of delayed type hypersensitivity were investigated in a 2,4-dinitrofluorobenzene contact sensitivity model. Various T cell subpopulations, suppressor T cells of afferent and efferent types, and an auxiliary T suppressor cells as well as a T effector cell of delayed type hypersensitivity were induced and the functions assessed in transfer experiments. Confirming the results of earlier experiments obtained with IFN-alpha, beta, the MuIFN-gamma N preparation and the rec. MuIFN-gamma R: enhanced the decreased response in animals sensitized with an antigen overload to an optimal response; inhibited the afferent-acting T suppressor cell in vivo and in vitro; inhibited the Ts-eff response; blocked the auxiliary T suppressor cell response after intravenous injection to recipients of Ts-eff cells on day 0 and 1; and did not suppress the activity of the T effector cell of delayed type hypersensitivity in vivo and in vitro (the MuIFN-gamma R was not tested). We conclude that IFN-gamma preferentially inhibited the T suppressor cell circuit of contact allergy. These results are similar to our observations on the inhibitory effects of a pure interferon-alpha, beta on the regulatory T suppressor cell circuit in contact allergy. Selective suppression of different T subpopulations by IFN-gamma may be an important regulatory mechanism in delayed type hypersensitivity.
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PMID:Inhibitory effects of interferon-gamma on the T suppressor cell circuit in contact sensitivity. 294 66

In this study we tested the effect of monoclonal antibodies (moAb) AN-18 to murine IFN-gamma on the generation of cytolytic T cells (CTL) from a homogeneous population of precursor cells (CTL-P). As responder cells, highly purified Lyt-2+ C57BL/6 lymph node T cells were used that had been positively selected by flow cytofluorometry on a cell sorter. Lyt-2+ cells were set up in bulk culture or in limiting dilution (LD) either with Con A or with P815 tumor cells as antigen and recombinant human interleukin 2 (rec.hIL 2) in the presence or absence of moAb AN-18 and tested for growth and development of CTL. The results show that moAb AN-18 but not the unrelated moAb AN-37 diminished or abrogated proliferative and cytolytic responses of Lyt-2+ lymphocytes to lectin and rec.hIL 2 in a dose-dependent manner. The inhibitory activity of the antibodies could be abolished by neutralizing moAb AN-18 with recombinant murine IFN-gamma (rec.mIFN-gamma) before their addition to culture. Kinetic analysis shows that the inhibitory effect of moAb AN-18 is only optimal when added at the beginning of culture or up to 48 hr after initiation. The frequencies of CTL-P responding either to Con A or to P815 tumor cells and rec.hIL 2 were reduced up to 10-fold in the presence of moAb AN-18. The inhibitory capacity of moAb AN-18 was also operative in cultures containing on the average one antigen-specific CTL-P. Together with the finding that activated CTL-P secrete IFN-gamma in response to rec.hIL 2 in a dose-dependent manner, the data suggest that endogenous IFN-gamma collaborates with exogenous IL 2 in the induction of CTL-P. The generation of CTL may therefore represent a case of autocrine growth regulation of normal lymphocytes, in which the same cell synthesizes and responds to its own factor.
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PMID:Monoclonal antibodies to interferon-gamma inhibit interleukin 2-dependent induction of growth and maturation in lectin/antigen-reactive cytolytic T lymphocyte precursors. 308 72

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

We studied the inhibitory activity of alpha-difluoromethylornithine (DFMO) and alpha-, recombinant beta-, and recombinant-gamma-interferons (alpha-, rec-beta-, and rec-gamma-IFNs) on in vitro growth of 3 established human urogenital tumors (KO-RCC-1 from renal cell carcinoma, Bewo from choriocarcinoma of the uterus, and HT-1197 from transitional cell carcinoma of the urinary bladder) and 16 primary renal cell carcinomas obtained by nephrectomy. Treatment with DFMO together with rec-IFN-gamma synergistically inhibited KO-RCC-1 cell growth in monolayer culture and in soft agar. The other two established cell lines were less susceptible to this treatment. Combination of DFMO and rec-IFN-gamma was more inhibitory than that of DFMO and either IFN-alpha or rec-IFN-beta. The polyamine content in KO-RCC-1 cells was decreased to a greater extent by combined treatment with DFMO and rec-IFN-gamma than that in Bewo and HT-1197 cells. The effect of these agents in 11 of the 16 primary renal cell carcinomas, which could show clonal growth in double layer soft agar, was examined. More than 50% inhibition of colony growth was seen in only one case (9%) treated with 5 mM DFMO alone and in 2 cases (18%) treated with rec-IFN-gamma alone (1,000 units/ml) but in 10 of the 11 cases (91%) with the combined treatment. Our results indicate that combined treatment with DFMO and rec-IFN-gamma can be more effective than that with either agent individually in inhibiting cell growth of human renal cell carcinoma in vitro.
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PMID:Enhanced inhibition of colony formation of human renal cell carcinoma in soft agar by the combination of alpha-difluoromethylornithine and recombinant gamma-interferon. 309 59

Human placental trophoblasts produce interferon (tro-IFNs) when stimulated with viral inducers. Since the antiviral and cellular functions of IFNs are partly mediated by the 2',5'-oligoadenylate synthetase (2-5A synthetase) pathway, the aim of the present study was to determine the basal and IFN-induced levels of 2-5A synthetase in villous trophoblast cultures. A considerable basal level of 2-5A synthetase was observed in syncytiotrophoblast cultures from both first and third trimester. In contrast no basal activity was detectable in placental fibroblast- and trophoblast-derived malignant cell lines (Far, FEG-3, and BeWo). Stimulation with tro-IFN-beta, -alpha and leucocyte-IFN (leu-IFN)-alpha increased the enzyme activity in first and third trimester human syncytiotrophoblast cultures. Treatment with recombinant-IFN (rec-IFN)-gamma significantly enhanced 2-5A synthetase activity in first trimester syncytiotrophoblast, but had no effect on third trimester syncytiotrophoblast. Tro-IFN-beta, -alpha and leu-IFN-alpha induced high levels of 2-5A synthetase activity in placental fibroblast, BeWo and FEG-3 cell-lines, whereas rec-IFN-gamma treatment did not induce 2-5A synthetase activity in any of these cells. No detectable 2-5A synthetase activity was found in the Far cell line. The capability of cells deriving from the fetoplacental unit to raise an antiviral response by the induction of 2-5A synthetase may be important in defending the fetus against viral infection from the mother. Furthermore 2-5A synthetase in cells of the fetoplacental unit may play a role in their normal growth and development.
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PMID:Basal and interferon-induced 2',5'-oligoadenylate synthetase activity in human placental trophoblast and trophoblast-derived malignant cell lines. 754 Jul 57

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

Interferons (IFNs) are important mediators of the immune system. Their antiviral activity is an integral part of the innate immune defence, but all IFNs have immune regulatory functions also. Besides rec.eq.IFN-beta detailed descriptions on other rec.IFNs were lacking and none of the proteins was available. To compare the equine IFNs and allow detailed studies on proteins and bioactivity, we performed the expression cloning of rec.eq.IFN-alpha, -beta and -gamma. To achieve maximal expression, a bacterial expression system was chosen. Additionally, rec.eq.IFN-beta and -gamma were expressed in mouse B-cells. The antiviral activity was characterised using different cell lines and equine viruses. The results demonstrate a broad antiviral activity of rec.eq.IFN-alpha being active against all viruses tested, including the equine herpesviruses EHV-1 and -4, while rec.eq.IFN-beta was only active using primary horse cells. Protection depended on viruses, cell lines, infectious doses, amount and time of IFN action prior to infection. While rec.eq.IFN-gamma did not act antivirally, it was effective as an immune modulator of monocytes in vitro. The implications of our findings on clinical immunology and virology, including therapeutic applications of equine IFNs will be discussed.
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PMID:Recombinant equine interferons: expression cloning and biological activity. 1182

This study was designed to determine the relative levels of gene transcription of selected pathogens and cytokines in the brain and spinal cord of 12 horses with equine protozoal myeloencephalitis (EPM), 11 with equine herpesvirus type 1 (EHV-1) myeloencephalopathy, and 12 healthy control horses by applying a real time pcr to the formalin-fixed and paraffin-embedded tissues. Total rna was extracted from each tissue, transcribed to complementary dna (cDNA) and assayed for Sarcocystis neurona, Neospora hughesi, EHV-1, equine GAPDH (housekeeping gene), tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10 AND IL-12 p40. S neurona cdna was detected in the neural tissue from all 12 horses with EPM, and two of them also had amplifiable cDNA of N hughesi. The relative levels of transcription of protozoal cdna ranged from 1 to 461 times baseline (mean 123). All the horses with ehv-1 myeloencephalopathy had positive viral signals by PCR with relative levels of transcription ranging from 1 to 1618 times baseline (mean 275). All the control horses tested negative for S neurona, N hughesi and EHV-1 cdna. The cytokine profiles of each disease indicated a balance between pro- and anti-inflammatory markers. In the horses with epm the pro-inflammatory Th1 cytokines (IL-8, TNF-alpha and IFN-gamma) were commonly expressed but the anti-inflammatory Th2 cytokines (IL-4, IL-6 AND IL-10) were absent or rare. In the horses with ehv-1 the proinflammatory cytokine IL-8 was commonly expressed, but IL-10 and IFN-gamma were not, and TNF-alpha was rare. Tissue from the control horses expressed only the gene GAPDH.
Vet Rec 2006 Sep 09
PMID:Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy. 1696 13