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Biomedical subjects

J Yodoi

Publications and source records attributed to J Yodoi.

At least 217 records · Page 12Linked to original sources

Differential regulation of the low affinity Fc receptor for IgE (Fc epsilon R2/CD23) and the IL-2 receptor (Tac/p55) on eosinophilic leukemia cell line (EoL-1 and EoL-3).

Two types of activation Ag, low affinity FcR for IgE (Fc epsilon R2)/CD23 and IL-2R (Tac/p55), were expressed and differently regulated on human eosinophilic leukemia cell lines (EoL-1 and EoL-3). Because the binding of IgE on EoL-3 cells was completely inhibited by H107 (anti-Fc epsilon R2/CD23 mAb) but not by irrelevant mAb, essentially all the low affinity Fc epsilon R2 on EoL-3 seemed to be the Fc epsilon R2/CD23 molecules. Both IL-4 and IFN-gamma enhanced the surface expression of Fc epsilon R2, whereas IL-1, IL-2, and IL-5 showed no effects, as determined by surface staining with anti-Fc epsilon R2 antibody (H107). In contrast to Fc epsilon R2 up-regulation, IL-4 and IFN-gamma showed a differential effect on the regulation of IL-2R (Tac/p55). Whereas IFN-gamma up-regulated the receptor expression of IL-2R/Tac, IL-4 did not. The result suggests that these lymphokines are involved in the different aspects of the activation pathway of the eosinophils. The possible role of Fc epsilon R2 and IL-2R on the function of eosinophils in allergic reaction is discussed.

Adjuvants, Immunologic↗

Low affinity IgE receptors: regulation and functional roles in cell activation.

The low affinity IgE receptors (Fc epsilon RII/CD23) homologous to animal lectins have the unique property of cleaving-off the extracytoplasmic portion as the soluble form (IgE binding factor; IgE-BF). Molecular analysis using Fc epsilon RII/CD23 cDNA proved that Fc epsilon RII is not unique to B lymphocytes but is expressed on a variety of cell lineages including T lymphocytes, macrophages and eosinophils. In these cell types, IL-4 is a general inducer of this molecule while IFN-gamma down-regulates B cell Fc epsilon RII/CD23 and up-regulates Fc epsilon RII/CD23 on macrophage and eosinophil cell lines. As predicted by the expression of Fc epsilon RII/CD23 in some HTLV-1(+) T cell lines, Fc epsilon RII/CD23 proved to be induced on normal peripheral T lymphocytes by IL-4 or IL-2 in the presence of additional permissive signals. As indicated by IL-2-dependent Fc epsilon RII/CD23 induction, there is an interesting bilateral co-regulation between Fc epsilon RII/CD23 and the 55 kDa chain of the IL-2 receptor complex with Tac antigen (IL-2R/p55(Tac]. Triggering of Fc epsilon RII/CD23 resulted in the enhanced expression of IL-2R/p55(Tac), whereas IL-2 enhanced the expression of Fc epsilon RII/CD23 in some systems. It is suggested that the triggering of cell surface Fc epsilon RII/CD23 by natural ligands is effectively buffered by soluble Fc epsilon RII/CD23 (IgE-BF).

Amino Acid Sequence↗

Molecular cloning and chromosomal assignment of a human perforin (PFP) gene.

Human perforin cDNA was isolated and the complete nucleotide sequence of the gene determined. The deduced amino acid sequence of human perforin showed 68.4% similarity to that of mouse perforin. RNA blot analysis of the human perforin gene revealed that the gene product is expressed preferentially in killer-type cells among cell lines tested, and in large granular lymphocytes among the peripheral blood mononuclear cells. In situ hybridization analysis with a human perforin cDNA probe revealed that the human perforin (PFP) gene is located on chromosome 17q11-21.

Base Sequence↗

Regulation of Fc epsilon receptor 2 (CD23) expression on a human eosinophilic cell line EoL3 and a human monocytic cell line U937 by transforming growth factor beta.

Regulation of low-affinity receptors for IgE (Fc epsilon R2/CD23) on a human eosinophilic cell line EoL3 and a human monocytic cell line U937 was studied using an anti-Fc,R2/CD23 monoclonal antibody H107 by flow cytometry. While platelet-activating factor, interleukin 4, and interferon gamma significantly augmented Fc epsilon R2/CD23 expression on both cell lines, transforming growth factor beta (TGF beta) inhibited both the basal level of Fc epsilon R2/CD23 expression and the enhanced Fc epsilon R2/CD23 expression induced by these reagents in dose- and time-dependent manners. However, TGF beta did not significantly suppress the high basal level of Fc epsilon R2/CD23 expression on RPMI 8866 cells. These results suggest that Fc epsilon R2/CD23 expression on EoL3 and U937 cells is regulated by various cytokines and growth factors, and that TGF beta plays an important regulatory role in IgE-mediated immune responses.

Antigens, Differentiation, B-Lymphocyte↗

Interferon and (2'-5')oligoadenylate enhance the expression of low affinity receptors for IgE (Fc epsilon R2/CD23) on the human monoblast cell line U937.

The regulation of low affinity IgE receptor (Fc epsilon R2/CD23) expression on the human monoblast cell line U937 was examined by an anti-Fc epsilon R2/CD23 monoclonal antibody (H107) and the cDNA probe for Fc epsilon R2/CD23. Alpha interferon (IFN-alpha) and its intracellular mediator, (2'-5')oligoadenylate (2, 5-A), induced Fc epsilon R2/CD23 expression on U937 with no significant increase of the Fc epsilon R2/CD23 mRNA. PMA and IFN-gamma increased both surface Fc epsilon R2/CD23 expression and the Fc epsilon R2/CD23 mRNA levels. IFN-alpha effectively induced 2, 5-A synthetase activity in U937 cells, whereas IFN-gamma induced little. The results suggest that the mechanisms of enhancement of Fc epsilon R2/CD23 expression on U937 cells by IFN-alpha and IFN-gamma are different and that 2, 5-A may play an important role in the Fc epsilon R2/CD23 expression on U937 cells induced by IFN-alpha.

2',5'-Oligoadenylate Synthetase↗

Heterogeneity in terms of interleukin 4-dependent regulation of Fc epsilon...receptor/CD23 expression on chronic B-lymphocytic leukemia cells.

To discriminate the stages of maturation arrest of leukemic B cells, we have investigated the cell surface expression of Fc epsilon RII (H107 antigen) on leukemic B cells from 6 patients with chronic type B-lymphocytic leukemia (B-CLL) by a double staining method combined with cytofluorometry, and their production of soluble Fc epsilon RII by an ELISA technique. Fc epsilon RII was expressed on mu+/delta- cells of case 5 as well as on mu+/delta+ cells of cases 1, 2 and 4, but not on mu+/delta+ cells in cases 3 and 6. The cultivation of leukemic cells with IL-4 not only increased the percentage of Fc epsilon RII+ cells but also enhanced the production of soluble Fc epsilon RII+ in most cases. However, IL-4 had no effects on mu+/delta-/Fc epsilon RII+ cells of case 5, which appeared to correspond to a rather late stage of normal B cell differentiation. Moreover, while leukemic B cells from case 1 spontaneously produced large amounts of soluble Fc epsilon R, the release seemed to be inhibited by an addition of IL-4. From our observations, it is speculated that IgM+/IgD+/Fc epsilon RII- leukemic B cells express surface membrane Fc epsilon RII and produce soluble Fc epsilon RII following stimulation with IL-4, and that IgM+/IgD-/Fc epsilon RII+ B-CLL cells may exist at some late stage of B cell differentiation.

Aged↗

Mitogenicity and down-regulation of high-affinity interleukin 2 receptor by YTA-1 and YTA-2, monoclonal antibodies that recognize 75-kDa molecules on human large granular lymphocytes.

A large number of interleukin 2 receptors lacking the Tac epitope (IL-2R/p75) were found to be constitutively expressed on the human large granular lymphocyte/natural killer cell line YT, which bears inducible IL-2R/p55 associated with Tac antigen. Two anti-YT IgG1 monoclonal antibodies, YTA-1 and YTA-2, recognizing different epitopes of the same 75- to 80-kDa molecule, were established. The 75-kDa antigen recognized by these monoclonal antibodies was strongly expressed on the large granular lymphocytes of normal peripheral blood mononuclear cells and on various lymphoid cell lines bearing IL-2R/p75. The YTA-1 and YTA-2 antibodies were mitogenic and were different from other mitogenic monoclonal antibodies such as anti-T3 (CD3), anti-T11 (CD2), and KOLT-2 (CD28). Further, they down-regulated the high-affinity IL-2R of peripheral blood mononuclear cells within 24 hr in culture. The relationship between the YTA-1/2 antigen and the IL-2R system is discussed.

Antibodies, Monoclonal↗

Formation of IgE-binding factors by lymphocytes of HIV-infected patients.

Peripheral blood mononuclear cells of human immunodeficiency virus infected patients were cultured in the presence or absence of 10 micrograms/ml human IgE, and culture filtrates were fractionated on IgE-Sepharose. IgE-binding factors were assessed in the acid eluate fraction from IgE-Sepharose by both rosette inhibition assay and radioimmunoassay. Among 22 cases studied, mononuclear cells from 9 patients formed IgE-binding factors in the absence of IgE, and those of 13 cases formed the factors upon incubation with IgE. The major cell source of IgE-binding factors was T cells. In 2 cases of human immunodeficiency virus infection, Fc epsilon receptors were detected on both Leu-2+ and Leu-3+ T cells.

AIDS-Related Complex↗

Soluble low affinity Fc receptors for IgE in the serum of allergic and nonallergic children.

IgE-binding factors are thought to have regulatory activity in in vitro IgE synthesis. To obtain evidence of the participation of IgE-binding factors in in vivo IgE synthesis, the serum level of low affinity Fc receptors for IgE (sFc epsilon RII) (IgE-BFs) was examined in 41 nonallergic children and in 37 allergic children whose serum IgE levels were significantly higher than those of nonallergic children. The serum level of sFc epsilon RII showed a marked age-dependent variation. It was highest in infants and then decreased gradually with age. The serum level of sFc epsilon RII in allergic children was significantly higher than that of nonallergic children in early childhood (1128.0 +/- 323.8 vs 777.3 +/- 227.0 pg/ml, p less than 0.01 in infants (less than 1 y) and 851.8 +/- 270.0 vs 579.4 +/- 197.1 pg/ml, p less than 0.05 in children aged 1-2 y) but not in older children (3-15 y). Three allergic infants (less than 1 y) with serum sFc epsilon RII levels higher than the mean + 1 SD (1451.8 pg/ml) of all allergic infants (less than 1 y) had serum IgE levels (geometric mean 125.9 IU/ml) significantly higher than the other seven allergic infants (less than 1 y) (geometric mean 5.6 IU/ml, p less than 0.05). A close positive correlation between the serum level of sFc epsilon RII and the absolute number of Fc epsilon RII(+) peripheral blood lymphocytes was observed (Spearman's rank correlation coefficient = 0.79, p less than 0.001 in 27 allergic and Spearman's rank correlation coefficient = 0.72, p less than 0.001 in 19 nonallergic children). In conclusion, serum sFc epsilon RII may be derived mainly from Fc epsilon RII(+) lymphocytes, and may have relationship to the increased production of IgE in early childhood (0-2 y).

Adolescent↗

Interleukin-2 receptor/p55(Tac)-inducing activity in porcine follicular fluids.

Very recently, it has been reported that interleukin-1 (IL-1) has an inhibitory effect on progesterone production by porcine granulosa cells in vitro. In the present study we investigated the presence of IL-1 or IL-1-like activity in porcine ovarian follicular fluids (FF) as the first step in elucidating the physiological role of IL-1 in follicular growth and maturation. Since IL-1 and IL-1-like substances have interleukin-2 receptor (IL-2R)/p55(Tac)-inducing activity (TIA), we determined the TIA in the FF by means of a highly sensitive TIA assay using flow cytometry. TIA was significantly higher (P less than 0.01) in the FF of small follicles than in those of medium-sized and large follicles. A significant negative correlation (P less than 0.05) was apparent between TIA and 17 beta-estradiol concentration in the FF. The conditioned media of porcine granulosa cells also showed TIA. Of these conditioned media, those from small follicles exhibited higher TIA than those from medium-sized and large follicles. TIA in the conditioned media decreased rapidly as the culture period was extended. Sex steroids such as 17 beta-estradiol, progesterone, testosterone, and androstenedione had no effect on IL-2R/p55(Tac) induction. These results indicate that porcine granulosa cells produce the IL-2R/p55(Tac)-inducing factor, the activity of which decreases in association with the maturation of the follicles. Because of the heterogeneity of IL-2R-inducing factors, the relationship between TIA in the FF and IL-1 should be elucidated. We discuss the possibility that this factor may play a role in follicular maturation and that enhancement of IL-2R/p55(Tac) expression by this factor may contribute to the local defense mechanism in ovarian follicles.

Androstenedione↗

Regulation of Fc epsilon R2/CD23 gene expression by cytokines and specific ligands (IgE and anti-Fc epsilon R2 monoclonal antibody). Variable regulation depending on the cell types.

The regulation of human low affinity FcR for IgE (Fc epsilon R2/CD23) and the soluble Fc epsilon R2 [IgE binding factor (BF)] of monocyte (U937), T (ED), and B (JIJOYE) cell lines was examined by anti-Fc epsilon R2 mAb (H107, Mab176) and the cDNA probe for Fc epsilon R2. The effect of IL-4 and IFN-gamma on Fc epsilon R2 regulation was variable among these three cell lines. IL-4 and IFN-gamma enhanced the Fc epsilon R2 gene expression and the production of Fc epsilon R2 and IgE-BF on U937, whereas IL-4 and IFN-gamma had no significant effect on the Fc epsilon R2 expression on ED. On JIJOYE, IL-4 enhanced the Fc epsilon R2 and IgE-BF production on both protein and mRNA levels. In U937 and JIJOYE cells, there was a marked increase of Fc epsilon R2 mRNA after combined stimulation with IFN-gamma and IL-4. However, in JIJOYE cells, there was a dissociation between the surface expression of Fc epsilon R2 and Fc epsilon R2 mRNA treated with IFN-gamma plus IL-4. In these cells. IFN-gamma even down-regulated the IL-4-induced expression of surface Fc epsilon R2. Stimulation of JIJOYE cells with both IFN-gamma and IL-4 resulted in the increase of the IgE-BF in the supernatant, suggesting that IFN-gamma enhanced the release of IgE-BF from Fc epsilon R2. The results indicated that Fc epsilon R2 and IgE-BF expression is regulated by IFN-gamma at least on two different levels: on transcriptional levels and the levels of cleavage of the surface Fc epsilon R2 to release soluble Fc epsilon R2 (IgE-BF). Ligands binding to the Fc epsilon R2 such as IgE and anti-Fc epsilon R2 mAb enhanced the surface expression of Fc epsilon R2 on these Fc epsilon R2(+) cell lines. This was mainly due to the surface accumulation of the receptors on JIJOYE and U937. However, the stimulation of ED by H107 and anti-Fc epsilon R2 mAb significantly enhanced the mRNA expression, indicating that Fc epsilon R2 synthesis may also be up-regulated by the specific ligands in some cell types.

Antibodies, Monoclonal↗

Differential effects on expression of IL-2 receptors (p55 and p70) by the HTLV-I pX DNA.

Abnormal expression of the low-affinity receptor for interleukin-2 (IL-2R) is a characteristic of the HTLV-I (+) leukemic T cells in adult T-cell leukemia (ATL). Despite the expression of IL-2R bearing Tac antigen (IL-2R/p55), leukemic cells of the majority of ATL patients do not proliferate in response to IL-2. In the human NK cell line, YT, as well as in ATL-derived T cells, the co-expression of IL-2R/p55 and the second IL-2R without the Tac epitope (IL-2R/p70) is required to produce high-affinity IL-2R. To study the effect of HTLV-I on both of the IL-2Rs, we transfected a fragment of HTLV-I containing the p40X gene into YT cells. One of the 2 transfected YT clones (YT/pX-5.1) had an increased level of expression of IL-2R/p55. In contrast, expression of IL-2R/p70 was unaffected, as determined by Scatchard analysis and the cross-linking study using 125I-IL-2. Our results show that the T-cell phenotype is not required for induction of IL-2R/p55 by p40X. We suggest that HTLV-I infection induces a disproportionate induction of IL-2R/p55 without significant enhancement of IL-2R/p70 expression, resulting in the predominant expression of low-affinity IL-2R in ATL. IL-2R/p70 may be a critical parameter determining the IL-2 reactivity of HTLV-I-infected T cells as well as of normal lymphocytes.

Antigens, Differentiation↗

IL-2 receptor(p55)/Tac-inducing factor. Purification and characterization of adult T cell leukemia-derived factor.

Many human T cell lymphotropic virus-I (HTLV-I) transformed T cells from adult T cell leukemia (ATL) patients continuously produce a humoral factor called ATL-derived factor (ADF) which induces IL-2R/Tac expression on T and NK cells. Using gel filtration, procion red Sepharose, DEAE, and reverse phase chromatography, we have purified ADF protein to homogeneity from 15 liters of serum-free culture supernatant of an HTLV-I(+) T cell line ATL-2. Purified ADF protein had the m.w. of 14,000 by SDS-PAGE and gel filtration, and its isoelectric point is around 5.0. ADF did not react with heteroantibodies against IL-1 alpha and IL-1 beta, which have also IL-2R/Tac-inducing activity on suitable target cells. Partial N-terminal amino acid sequence of ADF is different from other cytokines such as, IFN, BSF-2, and various IL whose cDNA has been cloned. Western blot analysis using rabbit antibodies against N-terminal 10mer synthetic peptide of ADF showed that IL-1 alpha and ADF are different proteins. ADF had its IL-2R/Tac-inducing activity not only on human NK-like cell line YT, but also on HTLV-I(+) T cells, such as ED. In contrast, macrophage-derived IL-1 lacked IL-2R/Tac-inducing activity on ED cells despite their IL-2R/Tac induction on YT, indicating that ADF and IL-1 have their effect via different receptors.

Adolescent↗

The human interleukin 2 receptor beta chain (p70). Direct identification, partial purification, and patterns of expression on peripheral blood mononuclear cells.

IL-2 binds to high- and low-affinity receptors on activated T cells. The high-affinity receptor was hypothesized to consist of the noncovalent association between the alpha chain (IL-2-R-alpha, p55) and a beta chain (IL-2-R-beta, p70), whereas the low-affinity receptor consists of p55 without p70. We now directly identify p70 as a 65-77-kD glycoprotein doublet. Preparative quantities of the IL-2/p70 complex have been isolated. Further, we demonstrate that p70 is the principal IL-2 binding protein on both resting CD4+ and CD8+ T cells and that both p70 and p55 can be induced on normal B cells and monocytes.

Antigens, Surface↗

Formation of IgE-binding factors by T cells of patients infected with human immunodeficiency virus type 1.

Peripheral blood mononuclear cells of 10 out of 26 patients with human immunodeficiency virus type 1 (HIV-1) released IgE-binding factors, as determined by two independent assays. The formation of the factors by the mononuclear cells was enhanced by incubation of the cells with homologous IgE. In the presence of IgE, peripheral blood mononuclear cells from 15 of the 26 patients formed a detectable amount of IgE-binding factors, whereas those of normal individuals of allergic rhinitis patients failed to do so. The major source of IgE-binding factors was the T cells of the HIV-1-infected patients. The CD8+ T cells from a HIV-1-infected patient formed IgE-binding factors upon incubation with IgE, and type II receptors for Fc epsilon were detected on both CD4+ T cells and CD8+ T cells in one of five patients studied. It was also found that culture supernatants of mononuclear cells from HIV-1-infected patients released soluble factors that induce normal human T cells to form IgE-binding factors. The results suggest that lymphocytes of some HIV-1-infected patients are activated to produce lymphokines regulating formation of IgE-binding factors.

AIDS-Related Complex↗