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Biomedical subjects

T Honjo

Publications and source records attributed to T Honjo.

At least 289 records · Page 16Linked to original sources
PubMed1988

Phenotypic conversion of T lymphoblastic lymphoma to acute biphenotypic leukemia composed of lymphoblasts and myeloblasts. Molecular genetic evidence of the same clonal origin.

Acute biphenotypic leukemia composed of lymphoblasts and myeloblasts developed in a patient with T lymphoblastic lymphoma (T-LBL) who had an anterior mediastinal mass. A novel myeloid cell line, termed TK-1, has been established from his peripheral blood after the leukemic conversion. The identical rearranged pattern of T cell receptor gamma-chain gene was observed among the DNAs derived from lymph node cells in the lymphoma phase, the myeloid cell line TK-1, and the subclones with different karyotypes (TK-1B and TK-1D), which showed that myeloid cells had been derived from the T-LBL of the same patient. This finding demonstrates that phenotypic conversion occurs in the clonally propagating tumor cells and suggests that some hematopoietic cells retain the capacity to adopt either lineage.

Acute Disease↗
PubMed1988

Molecular cloning and structure of the mouse interleukin-5 gene.

We isolated the chromosomal gene for mouse interleukin-5 (IL-5) from genomic libraries using a cloned mouse IL-5 cDNA as probe. Nucleotide sequence determination of the IL-5 gene and its flanking regions showed that the gene was composed of four exons. The sequence homologies of the exons 1, 2, 3, and 4 of the human and murine IL-5 genes are 70, 79, 85, and 77%, respectively. TATA-like and CAAT-like sequences were found 25 and 52 base-pairs, respectively, upstream of the transcription initiation site which was identified by S1 mapping analysis. The nucleotide sequences of the mouse and human IL-5 genes were about 70% homologous in the 5'-flanking region extending to 200 base-pairs upstream of the transcription initiation site, beyond which the homology declined rapidly. The sequence surrounding 50 base-pairs upstream of the initiation site was conserved among genes for other lymphokines: such as mouse granulocyte/macrophage colony stimulating factor, mouse IL-2, and mouse IL-4.

Amino Acid Sequence↗
PubMed1988

Introduction and expression of the interleukin 2 receptor (Tac) gene in hematopoietic stem cells with retrovirus vectors.

Retrovirus vectors provide an efficient carrier for introducing a gene into hematopoietic stem cells although expression of the inserted gene is not always successful. We constructed and compared three retrovirus vectors which carried cDNA encoding the light chain (Tac) of the interleukin 2 receptor under the control of different promoters; long terminal repeat (LTR) of murine retroviruses, the early promoter of simian virus 40 (SV40) and the promoter of the class I antigen gene of the major histocompatibility complex. We made three constructs containing these promoters. A first construct did not contain any additional promoter but LTR. A second and a third constructs contained the SV40 and the class I antigen gene promoters, respectively, in addition to LTR. The LTR of retrovirus vectors is derived from MoMuLV except that the U3 region of the 3'LTR of the third construct is derived from myeloproliferative sarcoma virus (MPSV). The second and third constructs were used for infection of bone marrow stem cells as the first construct was less efficient in expression of the interleukin 2 receptor in fibroblasts. Hematopoietic stem cells infected with the recombinant viruses were transplanted into lethally irradiated mice, and the expression of the transduced gene in hematopoietic progenitor cells was analyzed. Analysis of RNA isolated from spleen colonies showed that substantial amounts of interleukin 2 receptor mRNA were made by the construct containing the class I gene promoter and MPSV LTR. However, we could not detect any transcripts from the constructs containing MoMuLV LTR and SV40 early region promoter.

Animals↗
PubMed1988

Loss of genes on the long arm of chromosome 22 in human meningiomas.

It has been proposed that loss of genes at specific chromosomal loci leads to tumorigenesis in some human tumors. This type of oncogenesis was first demonstrated in retinoblastoma and Wilms' tumor. Recently, it has been reported that acoustic neuroma, ductal breast tumor, and renal cell carcinoma may be caused by the same mechanism. Cytogenetic studies demonstrated that some meningiomas have monosomy of chromosome 22. In addition, human meningiomas are often associated with bilateral acoustic neuroma in which specific loss of alleles on chromosome 22 has been demonstrated. Then, we compared constitutional and tumor genotypes from 14 cases of sporadic human meningiomas, using four polymorphic DNA probes on chromosome 22 (SIS, D22S1, D22S9, IGLC). Loss of constitutional heterozygosity was found in three of 11 informative cases. Two of the three meningiomas maintained constitutional heterozygosity at the IGLC locus and another one showed no loss of heterozygosity at IGLC or D22S9. These results suggest that loss of genes on chromosome 22 caused by either a partial deletion or a mitotic recombination at a locus distal to D22S9 plays an important role in tumorigenesis of the human meningioma.

Chromosome Deletion↗
PubMed1988

Immunological abnormalities in human interleukin-2 or interleukin-2/interleukin-2 receptor L chain transgenic mice.

We constructed two strains of transgenic mice that carry the cDNA of either human interleukin-2 (IL-2) or the L chain of its receptor under the control of the H-2Kd promoter. The IL-2 transgenic mice expressed human IL-2 mRNA in the thymus, spleen, bone marrow, lung, muscle, and skin. Human IL-2 protein was also detected in their sera. The IL-2 transgenic mice suffered from dermatitis and pneumonia. Immune responses of their spleen cells against antigens were significantly impaired whereas their spleen cells responded well to polyclonal lymphocyte activators, suggesting that constitutive expression of IL-2 might have affected the repertoire formation of T cells in the mice. The IL-2 receptor (IL-2R) transgenic mice were healthy. We crossed the IL-2 and IL-2R transgenic mice to yield hybrid mice expressing both the ligand and the receptor constitutively. The life span of the hybrid mice was remarkably shortened. In addition to several abnormalities found in the IL-2 transgenic mice, spleen cells of the hybrid mice showed the strong natural killer activity which was ascribed to a large number (18%) of Thy-1+/CD3-cells unique to their spleen.

Animals↗
PubMed1988

Molecular mechanism for the formation of the high-affinity complex of interleukin 2 and its receptor.

Interleukin 2 (IL-2) binds to its receptors with three distinct affinities, with Kd values of 10(-11) M (high), 10(-9) M (intermediate) and 10(-8) M (low). IL-2 responding cells express two proteins that bind IL-2, i.e. a 55 x 10(3) Mr protein (p55 or L chain), which has classically been known as the IL-2 receptor and a second 75 x 10(3) Mr chain (p75 or H chain) with intermediate affinity. Experiments were performed to clarify the mechanism of the high-affinity site formation. Crosslinking of human IL-2 with the high-affinity sites of human T lymphocytes yielded a 150 x 10(3) Mr ternary complex consisting of IL-2, L and H chains. The ternary complex with human IL-2 was formed on EL/Tac 3 cells expressing human L and murine H chains, although human IL-2 was unable to bind to the parental EL-4 cell, which does not express human L chain. The high-affinity ternary complex was stable during solubilization and fractionated by gel-filtration chromatography, and the numbers of these complexes were quantified by this method. The number of high-affinity sites on the CT/hR-1 cells, which express the human L, murine L and murine H chains, was almost constant even when either the human or murine L chain was blocked by specific antibodies in agreement with a previous observation. These results indicate that the L and H chains do not form a stable binary complex by themselves and that IL-2 binding induces the formation of the stable high-affinity ternary complex.

Animals↗
PubMed1987

Molecular cloning and structure of the human interleukin-5 gene.

We isolated the chromosomal gene for human interleukin-5 (IL-5) from human genomic libraries using a cloned human IL-5 cDNA as probe. Nucleotide sequence determination of the IL-5 gene and its flanking regions showed that the gene consisted of four exons and three introns. TATA-like and CAAT-like sequences reside 26 and 73 base pairs, respectively, upstream of the transcription initiation site identified by S1 mapping analysis. The 5'-flanking region of the IL-5 gene has sequences homologous with those of the corresponding regions of the genes for human granulocyte/macrophage colony-stimulating factor, murine IL-4, human interferon-gamma, and human IL-2. The intron-exon organization and location of the cysteine residue suggest that the IL-5 gene is phylogenetically related to the genes for the granulocyte/macrophage colony-stimulating factor, IL-4, and IL-2, although their amino acid sequences are not significantly conserved.

Amino Acid Sequence↗
PubMed1987

Regulation of murine IgE production in SJA/9 and nude mice. Potentiation of IgE production by recombinant interleukin 4.

Serum IgE levels were determined in different strains of mice with enzyme-linked immunosorbent assay by using rat monoclonal anti-murine IgE antibodies in normal and in Nippostrongylus brasiliensis-infected mice. After infection, serum IgE levels were high in BALB/c and CB-20, low in SJL/J and SJA/20 mice, and not detected at all in SJA/9 and nude mice. Surface IgE-positive cells were greatly increased in BALB/c and SJL/J mice after infection, but not in SJA/9 and nude mice. Most surface IgE-positive spleen cells were also surface IgM- and surface IgD-positive. When spleen cells from SJA/9 or nude mice were stimulated in vitro with lipopolysaccharide and recombinant interleukin 4 (formerly B cell-stimulating factor 1), IgE was produced and detected in the supernatants of these cultures. In addition, surface IgE-positive cells could be detected in these cultures. Most of the surface IgE-positive cells were surface IgM- and surface IgD-negative, unlike those seen in the spleens of Nippostrongylus-infected BALB/c and SJL/J mice. These observations show that SJA/9 and nude mice have IgE-producing precursor B cells, and after appropriate stimulation interleukin 4 can induce them to secrete IgE.

Animals↗
PubMed1987

A novel family of variable region genes of the human immunoglobulin heavy chain.

We isolated and sequenced six variable-region (V) gene segments of the human immunoglobulin heavy-chain (H) using the V71-2 segment as probe. These VH segments were more than 90% homologous to each other and less than 65% homologous to members of the three known VH families. The VH fragments hybridized to an identical set of restriction fragments on Southern blots of human placenta DNA. The new family was designated as the VH-IV family. The complexity of the VH-IV family was estimated to be at least nine genes, of which the sequenced seven were functional genes. The VH-IV family is homologous (76%) to the mouse Vh36-60 family.

Amino Acid Sequence↗
PubMed1987

The human IL-2 receptor gene contains a positive regulatory element that functions in cultured cells and cell-free extracts.

The 130-base pair fragment located between 220 and 90 base pairs upstream of the major transcription initiation site of the human interleukin 2 (IL-2) receptor gene had positive regulatory effect on the early promoter of simian virus 40 as well as its own promoter. This fragment seems to be responsible for not only cell-specific but also lymphokine-induced expression of the IL-2 receptor gene as assessed by DNA transfection. The same DNA fragment directed cell-specific transcription of the IL-2 receptor gene in extract of HTLV-I-infected T cells, MT-1, but not of Epstein-Barr virus-transformed B cells, CESS. The addition of small amounts of MT-1 extract to CESS extract resulted in specific expression of the IL-2 receptor gene, indicating that cell-specific expression is regulated by trans-acting molecules in MT-1 extract.

Animals↗
PubMed1987

Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissue-type mast cells.

We investigated the biological activity of IL-4 to murine connective tissue-type mast cells (CTMC). When purified peritoneal mast cells, typical CTMC, were incubated with pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM) in methylcellulose, about one-fifth of mast cells showed clonal growth. Recombinant IL-4 alone did not stimulate the clonal growth, and purified IL-3 alone induced development of a small number of tiny clusters. In contrast, addition of IL-4 to IL-3 increased the number of clusters by a factor of 10. The number and size of clusters induced by the combination of IL-3 and IL-4 were comparable to those of mast cell clusters induced by PWM-SCM. The present results indicate that IL-4 is an essential factor for in vitro clonal growth of CTMC.

Animals↗
PubMed1987

Interleukin 4 (IgG1 induction factor): a multifunctional lymphokine acting also on T cells.

A cDNA encoding the murine interleukin 4 (IL4) (IgG1 induction factor/B cell-stimulating factor no. 1) was recently cloned (Noma et al., Nature 1986.319: 640; Lee et al., Proc. Natl. Acad. Sci. USA 1986. 83: 2061). In this report we tested recombinant IL 4 in various T cell assays. It was found that IL 4 activated the murine T cell line CTLL to increased DNA synthesis but not to growth. It also activated normal concanavalin A (Con A)-stimulated T cells both to increased DNA synthesis and to growth. These T cell growth factor-like activities were not inhibitable by anti-IL 2 receptor antibodies. Evidence is given that both Lyt-2+ and L3T4+ T cells responded to IL 4. Finally, IL 4 acted synergistically with phytohemagglutinin or Con A on normal T lymphocytes as well as on thymocytes. These data, as well as those of others, imply that lymphokines have a broader range of activity than previously anticipated.

Animals↗
PubMed1987

Effect of breast feeding on responses of systemic interferon and virus-specific lymphocyte transformation in infants with respiratory syncytial virus infection.

In order to elucidate the mechanisms of breast-feeding-induced resistance to respiratory syncytial virus (RSV) infection, groups of breast-fed and bottle-fed infants with this infection were tested at the onset of illness and then again 1 and 2 weeks later for the presence of interferon (IFN) as well as of virus-specific lymphocyte transformation (LTF) activity. Alpha-IFN was detected in nine out of ten breast-fed infants, while it was found in only 11 out of 21 bottle-fed subjects. The rate of the detection of IFN was significantly higher in the former group (P less than .05). Mean levels of IFN activity were also higher in breast-fed infants than in bottle-fed subjects during the course of the illness. It was noted, however, that previous breast feeding elicited little enhancing effect on the IFN response of infants with RSV infection. Combining the two feeding groups, suppressed LTF activity to RSV seemed to be related to a positive IFN response, although the association was not statistically significant. These observations suggest that breast feeding has unique mechanisms for modulating the immune response of infants with RSV infection.

Breast Feeding↗
PubMed1987

T cell replacing factor/interleukin 5 induces not only B-cell growth and differentiation, but also increased expression of interleukin 2 receptor on activated B-cells.

A T-cell replacing factor (TRF)/interleukin-5 (IL-5) is a B-cell growth and differentiation factor. In the present study, we examined the role of TRF/IL-5 in the increase in the levels of interleukin-2 (IL-2) receptor expression on activated B-cells. High pressure liquid chromatography (HPLC)-purified TRF/IL-5 (B151-TRF) from TRF-producing T-cell hybridoma, B151K12, as well as recombinant TRF/IL-5 (rec-TRF) were used for the analysis. Maximum anti-2,4-dinitrophenyl (DNP) IgG antibody response of DNP-primed B-cells or polyclonal IgM secretion of B-cell tumor line BCL1 was seen when HPLC-purified B151-TRF was added or when suboptimal doses of B151-TRF were added to the culture in the presence of IL-2. Normal resting B-cells gave maximum anti-SRBC IgM PFC responses when HPLC-purified B151-TRF and IL-2 were present. The purified B151-TRF as well as rec-TRF also induced on B-cells increased expression of IL-2 receptors that react with monoclonal anti-murine IL-2 receptor antibody, PC61, and 125I-labelled IL-2. The numbers of functional high affinity IL-2 receptors on activated B cells increased at least 20-fold by culturing them with purified B151-TRF. Moreover, B151-TRF induced increase in the levels of steady-state mRNA for IL-2 receptor by approximately 8-fold. These results suggest that activated B-cells as well as BCL1-cells may express functional IL-2 receptors or closely related molecules when stimulated with HPLC-purified B151-TRF as well as rec-TRF.

Animals↗
PubMed1987

Transcription of IL-2 receptor gene is stimulated by ATL-derived factor produced by HTLV-I(+) T cell lines.

In HTLV-I transformed T-cell lines established from the patients with adult T-cell leukemia (ATL), there is a constitutive activation of the normal IL-2 receptor (IL-2-R) gene. These cell lines continuously produce an ATL-derived factor (ADF), an IL-2-R inducing factor without IL-2 activity. ADF enhances the expression of the IL-2-R through the augmentation of the IL-2-R mRNA in the HTLV-I(+) T-cell line (ED) as well as the NK cell line cells (YT). In YT cells, the transcriptional initiation of the promoter of the IL-2-R gene was enhanced by ADF but not by IL-2. Production of ADF by HTLV-I(+) T-cell lines may be involved in the abnormal expression of IL-2-Rs on these cells.

Cell Line↗