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Biomedical subjects

T Takemori

Publications and source records attributed to T Takemori.

At least 55 records · Page 3Linked to original sources
PubMed1993

The fetal thymus stores immature hemopoietic cells capable of differentiating into non-T lineage cells constituting the thymus stromal element.

Immature hemopoietic cell lines were established by transforming fetal thymocytes in vitro with a ts mutant of Abelson murine leukemia virus. They are positive for c-kit and IL-2R alpha but negative for lineage specific markers. Their TCR and Ig heavy chain genes are in germline configuration, and are expressed as germline gene transcripts. When these cell lines were stimulated in vitro with IL-1 their morphology changed into that of typical macrophages (M phi). Subsequent analysis of a particular clone, which displayed the morphological change at the highest efficiency among established cell lines, indicated that the clone possesses the capacity to differentiate into I-A-M phi capable of secreting several cytokines, and supporting the proliferation of fetal and adult thymocytes in vitro. If their surface markers are considered, their normal counterparts would be present in a minor subset of CD4-CD8- double-negative cells in the thymus in early development. The results raise the possibility that the thymic organ at an early stage of development stores immature hemopoietic cells capable of differentiating into a non-T lineage constituting the thymic stromal elements.

Abelson murine leukemia virus↗
PubMed1993

Characteristics of IgA antibodies against HIV-1 in sera and saliva from HIV-seropositive individuals in different clinical stages.

IgA antibodies were analysed in sera and saliva from 40 HIV-1 seropositive individuals. The level of total IgA in serum was elevated according to the progress of the disease. IgA antibodies against p24 and gp160 were detected in the asymptomatic phase of infection. However, they declined in the symptomatic phases in contrast with IgG antibodies. Interestingly, three patients in the symptomatic phase who showed high levels of IgA antibodies were all in relatively good clinical condition. The IgG and IgA antibodies in saliva declined in the symptomatic phase. The level of IgG anti-p24 antibodies in saliva correlated with that in serum, suggesting that IgG anti-p24 antibodies in saliva originated from those in the serum. These results indicate that IgA antibodies are regulated independently from IgG antibodies and that the mucosal immune system is impaired early in the symptomatic phase of HIV infection, which starts with mucosal impairment. Detection of IgA antibodies may be useful for prognosis of the disease in HIV-infected individuals. The results indicate also that treatment for the impaired IgA mucosal immune system should be taken into consideration.

AIDS-Related Complex↗
PubMed1992

Heavy chain variable (VH) region diversity generated by VH gene replacement in the progeny of a single precursor cell transformed with a temperature-sensitive mutant of Abelson murine leukemia virus.

Sequence analysis of a large number of DNA clones containing a functional heavy chain variable, diversity, and joining (VHDJH) complex generated by VH to VHDJH joining (VH gene replacement) in the progeny derived from a common precursor cell transformed with a temperature-sensitive (ts) Abelson murine leukemia virus (A-MuLV) indicates that endogenous VH gene replacement in vitro generates immunoglobulin gene joints distinct from those generated by the usual VH to DJH joining. Such joints keep the pentamer CAAGA at the 3' end of the donor VH segment and lack a recognizable D segment, as can be seen also in vivo. The results suggest that VH gene replacement participates in generating VH region diversity in vivo, as previously postulated. During the joining process, a unique VH gene was selected in all progeny cells, together with a single A nucleotide dominantly added to the junctional boundaries. The basis of these regulatory processes is discussed.

Abelson murine leukemia virus↗
PubMed1992

Immunoglobulin V gene replacement is caused by the intramolecular DNA deletion mechanism.

Circular DNA resulting from V gene replacement was studied with an A-MuLV transformed cell line containing ablts. This cell line undergoes V gene replacement at elevated temperatures in the immunoglobulin (Ig) heavy chain (H) gene. Examination of circular DNA revealed that a heptamer-related sequence (TACTGTG) within the coding region of VDJ was joined to the recombination signal sequence (RSS) of a germline VH segment. This provides direct evidence for a intramolecular DNA deletion mechanism for V gene replacement. In the pre-B cell line as well as in in vivo lymphocytes, unusual circular DNAs were found which were structurally similar to the V gene replacement circles. They represented excision products of the deletion type recombination between one complete RSS and a heptamer-like sequence in the Ig H region.

Animals↗
PubMed1992

Constitutive expression of the nef gene suppresses human immunodeficiency virus type 1 (HIV-1) replication in monocytic cell lines.

In order to study the effect of nef gene expression on viral replication in monocytic cells, we established monocytic (U937 and THP-1) cell transfectants constitutively expressing the human immunodeficiency virus type 1 nef gene. We constructed a plasmid expressing the nef gene derived from an infectious clone, NL432, under the control of SR alpha promoter which can drive a high level of gene expression. We found suppressed viral replication in nef-expressing monocytic cells, although a negative effect of nef was observed, with some variation depending on the virus strain and the cell. We also observed that the expression of the surface CD4 molecule is inversely related to the expression of the nef gene, especially in the U937 transfectants. These results indicate that the suppression of viral replication and the down-modulation of CD4 molecule by nef gene expression occur in monocytic cell lines as in T cell lines.

CD4 Antigens↗
PubMed1992

Characterization of a new subgroup of human Ig V lambda cDNA clone and its expression.

From a human bone marrow cDNA library, we have cloned and sequenced a gene which cross-hybridized with murine pre-B cell-specific gene 8HS-20 cDNA under the low-stringent condition. Sequence analysis predicted that this gene (YM-1) encoded 240 amino acids which had the basic structure of immunoglobulin lambda light chain. The 3' half of the YM-1 sequence was identical to the J lambda 2 C lambda 2 region except for four nucleotides. The 5' part of the gene had 87.6% sequence homology with the reported V lambda gene called T1. Comparison of the deduced amino acid sequences with representative members of the seven other V lambda subgroups showed considerable structural homology, but the maximum homology with these chains was 44%. Therefore, we conclude that YM-1 belongs to a new V lambda subgroup. Interestingly YM-1 showed higher homology with VpreB1 (56%) than with any of the other V lambda subgroups. By Southern blot analysis four to six cross-hybridizing V lambda bands were detected at high stringency. Expression of the V lambda gene was observed in immature as well as mature B cell lines without accompanying V-JC gene joining, suggesting that V lambda of the YM-1 locus is activated at the early stage of maturation.

Amino Acid Sequence↗
PubMed1991

[A community-based education program for serum cholesterol reduction in urban hypercholesterolemic persons--comparison of intensive and usual education groups].

A community-based education program was conducted for persons found to be hypercholesterolemic by screening during cardiovascular surveys, in an urban population, to evaluate the feasibility and effect of the program in primary prevention of coronary heart disease. The subjects were men and women aged 40-64 living in the suburbs of Osaka whose serum total cholesterol was between 240 and 299 mg/dl in both the 1988 and the 1989 surveys. Persons with hypothyroidism, those taking medication for hypercholesterolemia or hypertension, and with a history of stroke and coronary heart disease were excluded. Of the 111 persons who were eligible, 104 persons were recruited for the program on March, 1989. The 104 persons were randomly assigned to either an intensive education group (n = 51) or a usual education group (n = 53). For the intensive education group, seven education classes were held from April to November, 1989. Lectures, practice sessions, interviews, and spot cholesterol measurements were conducted in a local community center. The usual education group received a letter with results from the 1989 survey and dietary instruction in April 1989 and an education class in September 1989. Mean serum cholesterol in the intensive education group showed a 10.0 mg/dl greater reduction in September 1989 and a 9.0 mg/dl greater reduction in March 1990 than in the usual education group (p less than 0.05) while mean HDL-cholesterol did not change in either groups. The intensive education group reported a larger decrease in the dietary frequency of chicken egg, poultry skin and small fishes, foods which are rich in saturated fat and cholesterol. The frequency of fatty meat, butter and fish eggs was low in both groups and did not differ between the two groups after the one-year program. These results indicate that a population-based education program is feasible and effective in reducing serum total cholesterol of hypercholesterolemic persons.

Adult↗
PubMed1990

Two types of mu chain complexes are expressed during differentiation from pre-B to mature B cells.

Immunoglobulin mu chains synthesized in murine pre-B cells are known to be associated with surrogate light chains designated as omega (omega), iota (iota) and B34. In addition to these molecules, we identified the complexes of polypeptides (50, 40, 27 and 15.5 kd) associated with surface or intracellular mu chains of pre-B cell lines. Most of these polypeptides were continuously synthesized and associated with mu chains in virgin B cells lines, although some of them scarcely bound to the mu kappa dimer or mu 2 kappa 2 tetramer concomitantly present in the same clone or population. However, in mature B cells they were no longer detectable except B34. Cross-linking of micron chains on the surface of pre-B cells resulted in an increase in intracellular free Ca2+, indicating that the micron chain complex on the surface of pre-B cell lines acted as a signal transduction molecule. However, the receptor cross-linkage of pre-B cell lines did not induce the increased inositol phospholipid metabolism usually observed in virgin and mature B cell lines. These results suggest that, during the differentiation from pre-B to mature B cells, the cells express two types of mu chain complexes which exhibit different structures as a whole and possess different signal transducing capacities.

Abelson murine leukemia virus↗
PubMed1989

B cell precursors are present in the thymus during early development.

An in vitro system for transforming immature lymphoid cells present in the thymus at early development has been established. By phenotype analysis of the transformants obtained, we observed that B cell precursors, susceptible to Abelson murine leukemia virus (A-MuLV)- or Harvey murine sarcoma virus (H-MuSV)-induced lymphogenesis, were present at high frequency in the fetal thymus of BALB/c mice. These precursors recolonized alymphoid thymus lobes in vitro, as do T cell precursors. It was further observed that B precursors in the fetal liver were also capable of recolonizing alymphoid thymus lobes and were stored in a thymic environment. These results suggest that stroma cells of the fetal thymus may possess the capacity to support the growth of B precursors. On the other hand, B cell precursors sensitive to the viral transformation were undetectable in the fetal thymus of C57BL/6, although immunohistochemical analysis suggested their presence. However, in the fetal liver of the same strain, B precursors recolonizing alymphoid thymus in vitro were sensitive to the viral transformation. Based on these results, we will discuss both the role and fate of thymic B precursors. In addition, we also obtained T cell lymphomas at different stages of differentiation from the fetal thymus of C57BL/6 infected with A-MuLV or H-MuSV. These data indicate the usefulness of our system in establishing cell lines derived from intrathymic lymphogenesis at early development.

Abelson murine leukemia virus↗
PubMed1988

The analysis of immature lymphoid precursors stored in longterm bone marrow culture.

The long-term bone marrow culture system developed by Dexter (MBMC) is known to store immature lymphoid precursors capable of differentiating into mature B cells in irradiated or immunodeficient mice. It has been suggested that pre-B cells are not generated under such culture conditions, but that opinion was not based on any systematic analyses. In the present study under carefully controlled conditions, we observed that pre-B and pro-B cells were eliminated from the late stage of primary MBMC, and the former were not generated in recharged MBMC. Under appropriate conditions, these immature precursors in recharged MBMC generated in vitro immunoglobulin-positive (Ig+) cells to differentiate into antibody-forming cells upon stimulation with lipopolysaccharide (LPS). LPS-reactive B cells were observed in every 10th of the Ig+ cells, the frequency being essentially the same as that observed in normal B cells in different tissues. The immature B cell precursors generating LPS reactive cells were expressed in recharged MBMC at the frequency of 4.2 x 10(-6). A staining experiment showed that cells bearing AA4.1 were stored at the frequency of 10(-4)-10(-5). This frequency is thought to be similar to that of lymphoid precursors in recharged MBMC committed to differentiate along B lineage cells. Based on these results, we discussed the stage, nature, and mode of differentiation of immature lymphoid precursors stored in MBMC.

Animals↗
PubMed1987

A temperature-sensitive mutant of Abelson murine leukemia virus confers inducibility of IgM expression to transformed lymphoid cells.

Lymphoid cell lines were isolated that were inducible for the expression of surface immunoglobulin by shift from 35.5 to 39.5 degrees C after infection of mouse bone marrow cells with a mutagen-treated Abelson murine leukemia virus. Virus produced by one of the cell lines (ts49) transmitted the temperature-sensitive phenotype to new lymphoid transformants as well as to NIH/3T3 cells. In addition, the tyrosine autophosphorylating activity of the p120gag-abl protein synthesized in ts49-transformed cells was found to be temperature-sensitive. Shift experiments using ts49-transformed lymphoid cells showed that at 39.5 degrees C they synthesize increased amounts of mu and kappa chain RNA and protein, and that they can be further induced to secrete IgM when treated with lipopolysaccharide.

Abelson murine leukemia virus↗
PubMed1984

Specificity, duration and mechanism of idiotype suppression induced by neonatal injection of monoclonal anti-idiotope antibodies into mice.

Monoclonal antibodies detecting idiotopes on the germ line-encoded anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody B1-8 were injected at various doses into newborn mice and the expression of B1-8 idiotopes was measured in anti-NP responses in later life. Suppression was long lasting, and a 100-fold increase in the dose of anti-idiotope delayed recovery from suppression by 5-6 weeks. Upon injection of a single anti-idiotope, suppression was observed for all B1-8 idiotopes to various degrees. Certain idiotopically defined antibody phenotypes were much more efficiently suppressed, and later recovered from suppression, than others. This specificity pattern was observed at the level of both B and T cells from the manipulated animals, as demonstrated in cell transfer experiments in which such cells were mixed with normal T and B cells. In these experiments, there was evidence for suppression mediated by regulatory T (and possibly also B) cells. Whereas the B cells from the manipulated animals were idiotypically unresponsive in a T cell-dependent adoptive primary response, the frequency of lipopolysaccharide-reactive B cells expressing the target idiotype was only slightly reduced in these animals as compared to control mice. Together with data on the elimination of anti-idiotope antibody from the neonatally injected animals these results are interpreted in the following way: idiotype suppression is induced through the reaction of anti-idiotope with idiotopes expressed on the surface of newly generated B cells, at microgram concentrations of anti-idiotope. When the concentration of anti-idiotope fall below that level, recovery from suppression sets in. Two types of suppression are induced. The first, namely, direct blockade of B cell maturation, is short-lived. The second involves the induction of regulatory cells, perhaps through idiotope-bearing antibody V regions complexed by anti-idiotope. This type of suppression is long-lived and its specificity depends upon the distribution of the target idiotope in the antibody repertoire and/or peculiarities of the T cell receptor repertoire. It impinges on the selection of the B cell repertoire in the animal as expressed in T cell-dependent (and possibly other) responses and is thus hardly seen at the level of lipopolysaccharide-reactive (immature) cells. Idiotype suppression by regulatory cells may be perpetuated by antigen interacting with idiotypic antibodies on the B cell surface and may therefore play a role in establishing tolerance not only for the expressed antibody repertoire, but for self antigens in general.

Aging↗
PubMed1984

Mechanism of neonatally induced idiotype suppression and its relevance for the acquisition of self-tolerance.

We present an analysis of the elimination of a monoclonal anti-idiotope antibody injected into C57BL/6 mice on the day of birth. During the first 4 weeks of life the antibody is eliminated from the circulation with a slow half-life, ranging from 15-18 days. This finding makes sense biologically as the animals depend at that time on maternally transmitted antibodies. After 4 weeks elimination speeds up considerably. The rate of elimination appears to be the same for a 1 microgram and a 100 microgram dose. The elimination data and previous results on the specificity, duration and cellular basis of idiotype suppression induced by the monoclonal anti-idiotope fit into the following model of idiotype suppression, which is in good accord with other experimental evidence on idiotype and allotype suppression in the literature: suppression depends strictly on the concentration of anti-idiotope in the cellular environment. As long as it is in the microgram range, the generation of idiotope-bearing B cells from pre-B cells is prevented. The system recovers quickly from this type of suppression, as soon as the concentration of anti-idiotope falls below that range. A second type of suppression is also induced in the anti-idiotope-treated animals. It is long-lived (8-10 weeks longer that the first type), has a peculiar specificity in that it affects, in our particular case, only a certain subset of the antibodies bearing the target idiotope, and involves regulatory T (and possibly B) cells which prevent the functional maturation of B cells expressing those antibodies in the animal. Suppression of this type also depends strictly on anti-idiotope concentration and is induced either at the time when the generation of idiotope-bearing B cells from pre-B cells is still inhibited or just thereafter, when such cells begin to appear in the system and the anti-idiotope concentration is still at a few hundred nanograms per ml. Experimental evidence indicates that in the induction of suppression, the primary target of the anti-idiotope are idiotope-bearing antibodies variable regions. We assume that those variable regions, complexed by anti-idiotope are the inducers of regulatory (suppressive) T cells. Idiotype suppression may also be induced upon interaction of antibody variable regions (and possibly other receptors) with ligands other than anti-idiotypic antibodies. We, therefore, think that idiotype suppression not only establishes self-tolerance within the antibody system, but is a mechanism of self-tolerance in general.

Animals↗
PubMed1983

The expression of a set of antibody variable regions in lipopolysaccharide-reactive B cells at various stages of ontogeny and its control by anti-idiotypic antibody.

An analysis is presented in which we measure the expression of a subset of antibody variable (V) regions in lipopolysaccharide (LPS)-reactive precursor B cells at various stages of ontogeny. The V regions were characterized by hapten (4-hydroxy-3-nitrophenyl)acetyl (NP)-binding specifity and/or expression of idiotypic determinants whose genetic basis had been explored in previous studies. Only V regions containing the V lambda 1 domain were considered: this allowed an unequivocal determination of idiotopes and reduced heterogeneity in the system essentially to the multiplicity of VH and D genes. It was found that approximately every fourth lambda 1-bearing LPS-reactive splenic B cell produces an NP-binding antibody. Approximately 1 in 40 lambda 1-bearing cells expressed an idiotope (Ac38) which is encoded by V lambda 1 and a set of related VH genes in combination with D and J elements. Of these cells, only a minority produce an NP-binding antibody and a few percent of the latter express a second idiotope (Ac146) which is known to be restricted to a subset of Ac38-positive, NP-binding humoral antibodies. All these frequencies are in good accord with previous analyses of anti-idiotope-induced antibodies in the serum. They can be easily accommodated into a simple model of random selection of VH genes in LPS-reactive B lymphocytes. The frequencies of the V regions under study were essentially the same in LPS-reactive B cells from spleens of adult and newborn animals and in LPS-reactive B cells generated from bone marrow pre-B cells in vitro. In the case of the latter cells the frequencies were independent of the absence or presence of T cells in the culture system. While we could thus detect, in naive mice, neither positive nor negative selection of the cells from the time of their generation in the bone marrow until their arrival in the periphery, negative selection is in principle possible: the presence of microgram amounts of anti-idiotope antibodies during maturation from pre-B to B cells specifically blocks the appearance of idiotope-bearing LPS-reactive cells in vitro. The potential physiological role of the latter effect in the sense of self-stabilization of the expressed antibody repertoire in ongoing immune responses and the possibility that frequency determinations in LPS-reactive B cells may be not representative for the repertoire expressed in the population of mature B cells is discussed.

Aging↗
PubMed1983

The immune response against anti-idiotope antibodies II. The induction of antibodies bearing the target idiotope (Ab3 beta) depends on the frequency of the corresponding B cells.

In the present study we use two monoclonal anti-idiotope antibodies (Ac38 and Ac146; Ab1) against the germ line-encoded, lambda 1 chain-bearing and (4-hydroxy-3-nitrophenyl)acetyl (NP)-binding antibody B1-8 (Ab1) for the induction of complementary antibodies (Ab3) and ask the question to what extent antibodies bearing B1-8-like idiotopes (Ab3 beta) are represented in the Ab3 population. In this experimental system, Ab3 beta is distinguished from the remaining Ab3 population (Ab3 alpha) by three properties which Ab3 beta may share with B1-8: (a) the binding of NP, (b) the binding to Ac146 (if induced by Ac38) or the binding to Ac38 (if induced by 146) and (c) that they carry lambda 1 chains. Antibodies with all three properties are induced in low amounts by both anti-idiotopes. Also, Ac146 induces only Ab3 alpha (bearing kappa chains and not binding NP and Ac38). In contrast, Ac38 triggers almost exclusively a lambda 1 chain-bearing response, i.e. Ab3 beta. The response has an unusually large size, reaches its maximum after a week and is long-lasting. An analysis at the level of lipopolysaccharide-reactive precursor B cells demonstrates that, in this case, cells expressing Ab3 beta occur at exceedingly high frequency (approximately equal to 10(-3] and are at least 10 times more frequent than cells expressing Ab3 alpha. The high frequency of Ab3 beta-expressing cells correlates with the contribution of several VH, D and J genes to the expression of this particular idiotope. In the case of the Ac146 anti-idiotope antibody, the response is dominated by Ab3 alpha. Ab3 beta represents less than 10% of the total response, reaches maximal levels 2 weeks after immunization and declines rapidly. This correlates with a low frequency of precursor B cells expressing Ab3 beta (approximately equal to 10(-5] and a restriction of the corresponding idiotope to rare VH-D combinations, caused presumably by a stringent contribution of the H chain to this idiotope which covers the NP-binding site. Our data suggest that anti-idiotypic antibodies (Ab2) against Ab1 will preferentially induce antibodies idiotypically related to Ab1 if the corresponding idiotopes are expressed in high frequency in the B cell compartment. This is expected in cases where Ab2 recognizes an idiotope that can be formed by many germ line-encoded VH-D-VL-combinations.

Animals↗
PubMed1982

The immune response against anti-idiotope antibodies. I. Induction of idiotope-bearing antibodies and analysis of the idiotope repertoire.

In the present analysis we dissect the idiotype repertoire, independently of hapten-binding specificity, by immunizing different strains of mice with cross-linked monoclonal anti-idiotope antibodies against antibody B1-8. B1-8 is a monoclonal antibody with specificity for the hapten (4-hydroxy-3-nitro-phenyl)acetyl (NP) and carries a germ line gene-encoded variable region. The results demonstrate that the expression of B1-8 idiotopes and their association with each other and with NP-binding specificity are strain-specific. Certain idiotopes are expressed on antibodies differing in antigen-binding specificity, whereas one of the idiotopes appears strictly associated with NP-binding antibodies. The genetic analysis provides strong evidence that the strain specificity of the idiotope repertoire is a result of V region polymorphism in the mouse.

Animals↗