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T Sado

Publications and source records attributed to T Sado.

At least 73 records · Page 4Linked to original sources
PubMed1991

Characterization of thymic prelymphoma cells that develop during radiation-induced lymphomagenesis in B10 mice.

An intrathymic (i.t.) injection assay on B10.Thy-1 congenic mice was used to demonstrate that thymic prelymphoma cells developed first within mouse thymus 4 to 8 days after split-dose irradiation and were present in more than 63% of the test donor mice thymuses examined 21 and 31 days after irradiation. For the characterization of these thymic prelymphoma cells, thymocytes from B10.Thy-1.1 mice sampled 1 mo after irradiation were stained with J11d mAb and mAb against TL-2 (thymus-leukemia) antigen which is not expressed on normal thymocytes of the B10.Thy 1.2 and B10.Thy 1.1 strains but does appear on thymocytes of split-dose irradiated mice. These cells were sorted into subpopulations, samples of which were injected into recipient thymuses to determine which subpopulations contained thymic prelymphoma cells. Results showed that the prelymphoma cells were located in the J11d+TL-2+ cells. These prelymphoma cells were further characterized phenotypically as to their expression of the CD4 and CD8 antigens, which demonstrated that the thymic prelymphoma cells were present in the CD4-CD8- and CD4-CD8+ thymocyte subpopulations mainly and in the CD4+CD8+ subpopulation. The experiments on i.t. injection of a graded quantity of TL-2+ thymocytes from individual mice suggest that not all TL-2+ cells undergo neoplastic initiation and that prelymphoma cells may develop infrequently from one or more TL-2+ cells by genetic or epigenetic changes.

Animals↗
PubMed1991

Bone marrow-thymus interactions during thymic lymphomagenesis induced by fractionated radiation exposure in B10 mice: analysis using bone marrow transplantation between Thy 1 congenic mice.

Bone marrow transplantation (BMT) experiments were conducted using B10.Thy 1 congenic mice to explore the nature of bone marrow-thymus interactions during thymic lymphomagenesis induced by fractionated whole-body X-irradiation (FX). BMT from normal Thy 1 congenic donors into FX-treated recipients one day after FX-treatment resulted in the suppression of tumor development; the suppression being exponentially proportional to the increasing number of bone marrow cells injected. The suppression of tumor development by BMT was shown to be due to prevention of the appearance of prelymphoma cells. BMT from FX-treated donors, which are deficient in pre T cells, into lethally (9 Gy) irradiated Thy 1 congenic recipients resulted in the development of high incidence of thymic lymphomas most of which (approximately 76%) were host-derived, whereas no lymphomas were recovered from the recipients of normal bone marrow. These results suggest that intrathymic T cell precursors which initially repopulate the depleted thymus are prone to undergo preneoplastic changes in the absence of recruitment of more primitive T cell precursors (pre T cells) from the bone marrow but they undergo normal differentiation when large number of pre T cells are available. It was concluded that primary cause of the FX-induced thymic lymphomagenesis was a shortage in supply of pre T cells from the bone marrow to the depleted thymus, which caused differentiation arrest of the progeny of regenerating intrathymic T cell precursors, followed by development of prelymphoma cells that eventually evolve into autonomous lymphoma cells within the thymus.

Animals↗
PubMed1990

Manifestation of allo H-2-restriction specificity by self H-2-restricted T cells.

Previous study has demonstrated that a considerable number of antigen-specific, allo H-2-restricted CTLPs could be recovered from normal lymphocytes. Experiments were conducted to examine whether antigen-specific, self H-2-restricted T cells could also manifest allo H-2-restriction specificity. Non-H-2-specific, self H-2-restricted CTLs were induced in the microcultures with a limited number of responder spleen cells from B10(H-2b) mice that had been primed with C3H.SW(H-2b) spleen cells. Two hundred thirteen non-H-2-specific CTLs generated in limiting dilution culture condition were assayed for cross-reactivity against TNP-modified and unmodified allogeneic targets of 10 different H-2 haplotypes. Of these CTLs, 29 (14%) were cross-reactive to a TNP-modified allogeneic target and seventeen (8%) to an unmodified allogeneic target. The quantitative analysis for cross-reactivity of non-H-2 specific, self H-2-restricted CTLs reveals a significant number of CTLs that were cross-reactive with either alloantigen or antigen (TNP) plus allo H-2. Furthermore, CTL clones with triple specificities including self H-2-restriction specificity, allo-reactivity, and allo H-2 restriction specificity were also found. These results indicate that antigen-specific, allo H-2-restricted T cells are distinct not only from alloreactive T cells but also from antigen-specific, self H-2-restricted T cells. Significance of the manifestation of allo H-2 restriction specificity by self H-2-restricted T cells is discussed in regard to the generation of T cell repertoire.

Animals↗
PubMed1990

Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation.

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells.

Animals↗
PubMed1990

Homogenous junctional sequence of the V14+ T-cell antigen receptor alpha chain expanded in unprimed mice.

Nucleotide sequences of VJ (variable-joining) junctional regions of V14+ alpha-chain T-cell receptor genes show that most V alpha 14+ T cells use one alpha chain (V alpha 14J alpha 281 with a one-nucleotide N region, which is frequently used in keyhole limpet hemocyanin-specific suppressor T-cell hybridomas) in unprimed mice. Moreover, the frequency of this alpha-chain expression was greater than 1.5% of the total alpha chains found in laboratory strains, including B10 congenic mice. This is about 10(4) times higher than was expected. The V14J281 alpha-chain expression was relatively low but was significant in CD4+/CD8+ immature thymocytes and became quite high in mature single-positive T cells, implying that this alpha chain is selected during T-cell maturation. V14J281 expression increased with time after birth and reached a maximum at around 5 weeks of age. The ligand seems to be a self molecule and to be present in laboratory strains but to be absent in a wild mouse, Mus musculus molossinus, because bone marrow chimeras clearly showed that bone marrow cells derived from Mus musculus molossinus negative for this alpha chain raised V14J281-positive T cells in a C57BL/6 environment. The above results suggest that there are some selection mechanisms for this cell type other than those for conventional alpha beta T cells and also that the homogenous VJ junction of the V14J281 alpha chain plays a pivotal role in the selection of the T cell and its ligand reactivity.

Animals↗
PubMed1989

Immunohistological analysis of immigration of thymocyte-precursors into the thymus: evidence for immigration of peripheral T cells into the thymic medulla.

The immigration route of thymocyte precursors into the thymic microenvironment was examined in various experiments using two strains of mice (B10.Thy-1.1 and C57BL/6) that were identical in H-2 and different in Thy-1 locus. The experiment of thymus grafting revealed that there were two types of thymocyte precursors; one immigrated into the cortex and vigorously proliferated and the other directly immigrated into the medulla. Such a direct immigration of host-type cells into the medulla of the grafted thymus was not observed, when thymus was grafted into young adult nude mice having no T cells. When bone marrow cells were iv injected into intact mice, the direct immigration of donor-type cells was observed only in the cortex, not in the medulla. In parabiotic mice, the immigration of partner's cells into the medulla was observed independently before the proliferation of partner's cell in the cortex. These findings taken together indicate that peripheral T cells directly immigrate into and recirculate through the thymic medulla.

Animals↗
PubMed1988

Study on the possible factors influencing the expression of H-2 restriction specificity and Ir phenotype of antigen-specific proliferative T cells with various types of radiation chimeras.

To better understand the factors described previously as influencing the manifestation of H-2 restriction specificity and Ir phenotype of T cells from radiation bone marrow chimeras, we also examined H-2 restriction specificity (Ir phenotype) of antigen (DNP-OVA, (T, G)-A-L, (H, G)-A-L)-specific proliferative T cells generated in various types of H-2 incompatible radiation chimeras prepared under our specific-pathogen-free (SPF) condition. The results indicated the following: (a) T cells generated in F1----parent bone marrow chimeras preferentially manifested host-type H-2 restriction specificity and Ir phenotype, regardless of the radiation dose (8.70 vs 11.59 Gy); (b) T cells recovered from twice-reconstituted F1----(PA----PB) chimeras manifested primary host (PB)-type Ir phenotype; (c) T cells which were recovered from (B10.Thy-1.1 X B10.BR.Thy-1.1)F1----parent (Thy-1.2) bone marrow chimeras and treated with anti-Thy-1.2 plus complement to deplete host-derived T cells still manifested preferentially the restriction specificity for host-type H-2; (d) PA-derived T cells which had differentiated in a fully allogeneic host (PB) environment of (PA + PB)----PB chimeras manifested fully allogeneic host-type Ir phenotype; (e) T cells from F1----parent chimeras that were prepared with 13-day fetal liver cells also manifested host H-2-restricted Ir phenotype; and (f) host preference for Ir phenotype of antigen-specific proliferative T cells was observed even in the case of F1----parent bone marrow chimeras reconstituted with "intact" bone marrow cells. The data suggest that thymic APCs, surviving host T cells or the source of stem cells (adult bone marrow vs 13-day fetal liver), do not necessarily play a significant role in the manifestation of H-2 restriction specificity and Ir phenotype of T cells generated in H-2 incompatible radiation chimeras.

Animals↗
PubMed1988

Immediate and long-term effects of radiation on the immune system of specific-pathogen-free mice.

Studies on the immediate and long-term effects of radiation on the immune system of specific-pathogen-free mice are summarized in this paper. There was a striking difference in the radiation response of lymphocyte subsets; B cells consist of a fairly radiosensitive homogeneous population, whereas T cells consist of a large percentage (greater than 90 per cent) of radiosensitive and a small percentage (less than 10 per cent) of extremely radioresistant subpopulations. Ly 1+ and Ly 2+ lymphocytes appear equally radiosensitive, although the percentage of radioresistant cells was slightly larger for the former (approximately 5.5 per cent) than the latter (approximately 2.5 per cent). There was a significant strain difference in the radiosensitivity of immune-response potential in mice; immunocompetent cells of C3H mice were more radioresistant than those of BALB/c, C57BL/6, and B10.BR mice. Studies on the long-term effect of radiation on immune system in mice indicated no evidence for accelerated ageing of the immunologic functions when radiation exposure was given to young adults. Preliminary results on the enhancing effect of low dose radiation on cytotoxic T cell response in vitro are also discussed.

Animals↗
PubMed1988

Acquisition of repertoires of suppressor T cells under the influence of macrophages.

Acquisition of repertoires and genetic restriction specificities of suppressor T cells (Ts) and their factors were studied by using full allogeneic radiation bone marrow chimera and H-2 congenic pairs, B10.A(3R) and B10.A(5R), which received conventional or cloned macrophages by cell transfer. Suppressor T-cell factor (TsF) from C3H----C57BL/6 or C57BL/6----C3H chimera suppressed only donor but not host-type responses of either C3H or C57BL/6, in an antigen-specific fashion. However, if chimera mice were given conventional or cloned macrophages of the host type, the chimera TsF in turn suppressed both the responses of C3H and C57BL/6 mice but not those of the third party, BALB/c, indicating that macrophages are responsible for the acquisition of host restriction specificity. Similarly, B10.A(5R) mice developed I-Jb restricted Ts or TsF when the B10.A(3R) macrophage cell line was injected at the time of antigen priming. The reverse was also true. B10.A(3R) mice did generate I-Jk restricted Ts when they received the B10.A(5R) macrophage cell line. Thus, the results clearly demonstrated that B10.A(3R) or B10.A(5R) mice potentially possessed their ability to express both I-Jk and I-Jb determinants and that repertoires and genetic restriction specificity of Ts and their TsF were acquired at a macrophage level at the time of antigen-priming.

Animals↗
PubMed1988

Influence of age on the proliferation and peripheralization of thymic T cells.

Bone marrow cells obtained from B10.Thy-1.1 mice (H-2b, Thy-1.1) were injected directly into the thymus of C57BL/6 mice (H-2b,Thy 1.2) of various ages. Thymocyte precursors in the injected donor-bone marrow cells could proliferate in the thymic microenvironment in the following manner: first, preferentially proliferating into the subcapsular cortex; and second, spreading to the whole layer of the cortex, a portion of them gradually moving into the medulla. The proliferation of donor-type thymocytes was most pronounced when intrathymic injection of bone marrow cells (ITB) was performed in newborn mice and especially prominent in week-old mice; it took approximately ten weeks for donor-type thymocytes to finish the whole course of proliferation, differentiation, and emigration to the periphery. When ITB was performed in mice 4 weeks of age and older, the proliferation of donor-type thymocytes was retarded at onset, less pronounced in magnitude, and disappeared earlier. Emigration of donor-type T cells from the thymus to the peripheral lymphoid tissues occurred most rapidly when ITB was performed in newborn mice, and these T cells continued to reside thereafter in the peripheral lymphoid tissues. However, when ITB was performed in mice 4 weeks of age and older, the number of emigrated T cells in the spleen decreased (about a tenth of that in newborn mice) and, moreover, these T cells resided only transiently in the spleen. It was suggested that T cells emigrating from the thymus of mice from newborn to 2 weeks of age are long-lived, whereas those from the thymus in mice 4 weeks of age and older are short-lived. However, when 4-week-old young adult mice were treated by irradiation or hydrocortisone, the thymic capacity was enhanced in terms of proliferation and peripheralization of thymocytes, and emigrated T cells became long-lived.

Adrenal Cortex Hormones↗
PubMed1987

Development of prelymphoma cells committed to thymic lymphomas during radiation-induced thymic lymphomagenesis in B10 mice.

Intrathymic (i.t.) as well as i.p. injection of thymus cells from B10.Thy-1.1 mice manifesting overt thymic lymphomas, 4 months after split-dose irradiation, into B10.Thy-1.2 recipient mice resulted in the development of donor-type T-cell lymphomas, indicating that they contained "autonomous" lymphoma cells. In contrast, injection of thymus cells from apparently nonleukemic mice 1 month after split-dose irradiation resulted in the development of donor-type tumors only when they were injected i.t., suggesting that thymus cells from these mice contained "preneoplastic" cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment. These "thymus-dependent" preneoplastic cells were termed "thymic prelymphoma cells." With the use of i.t. injection assay, it was shown that these thymic prelymphoma cells were detected in 26.1% (6 of 23) of the test donor thymuses when examined at 14 days and in more than 63% (15 of 24 and 14 of 22) when examined at 21 and 31 days after irradiation. To examine the possibility that thymic prelymphoma cells might appear first in the bone marrow before they become detectable within the thymuses of the split-dose-irradiated mice, bone marrow cells from B10.Thy-1.1 donors recovered at 8, 14, 21, and 33 days after split-dose irradiation were also injected i.t. into B10.Thy-1.2-recipient mice. The results indicated that none of these recipients developed donor-type T-cell lymphomas, suggesting that bone marrow is not the first site of the appearance of thymic prelymphoma cells.

Animals↗
PubMed1987

Characterization of virus-specific cytotoxic T cell clones from allogeneic bone marrow chimeras.

We established several H-2-restricted lymphocytic choriomeningitis virus (LCMV)-specific cytotoxic T cell clones from spleens of virus-primed C57BL/6 or C57BL/10 (H-2b) and B10.BR (H-2k) mice and from allogeneic C57BL/10----B10.BR and B10.BR----C57BL/10 bone marrow chimeras. Two T cell clones of H-2b origin and restricted to H-2b, 3 of H-2k origin and restricted to H-2k were compared with two clones each derived from the two types of chimeras. Their surface phenotype was found to be Lyt-2+, L3/T4- and KJ16-133+ (2 of 9). Clones from chimeras expressed bone marrow donor H-2 and are restricted to the recipient H-2. H-2k-restricted clones were all specific for Kk whereas all H-2b-restricted clones were specific for Db. These restriction specificities could be further defined by the blocking activity of various monoclonal anti-H-2 antibodies. Interestingly the anti-H-2Db antibodies blocked the restricted virus-specific killing activity of the clones derived B10.BR----C57BL/10 chimeras much more effectively than the activity of the clones derived from conventional H-2b mice. The various clones differed with respect to their fine specificity for LCMV strains. The 3 clones of conventional B10.BR origin only recognized LCMV-WE but not LCMV-Armstrong, Aggressive or Docile; H-2b-restricted conventional clones recognized target cells infected with all LCMV strains except LCMV-UBC-Docile; the T cell clones from the bone marrow chimeras recognized with one exception all LCMV strains tested.

Animals↗
PubMed1986

Limiting dilution analysis of the stem cells for T cell lineage.

Stem cell activities of bone marrow, spleen, thymus, and fetal liver cells for T cell lineage were studied comparatively by transferring the cells from these organs through i.v. or intrathymus (i.t.) route into right leg- and tail-shielded (L-T-shielded) and 900 R-irradiated recipient mice, which were able to survive without supplying hemopoietic stem cells. Cells from B10.Thy-1.1 (H-2b, Thy-1.1) mice were serially diluted and were transferred into L-T-shielded and irradiated C57BL/6 (H-2b, Thy-1.2) mice, and 21 days later the thymus cells of recipient mice were assayed for Thy-1.1+ cells by flow cytofluorometry. The percentage of recipient mice possessing donor-type T cells was plotted against the number of cells transferred, and the stem cell activity in each cell source was expressed as the 50% positive value, the number of donor cells required for generating donor-type T cells in the thymuses of 50% of recipient mice. In i.v. transfer experiments, the activity of bone marrow cells was similar to that of fetal liver cells, and about 100 times and nearly 1000 times higher than those of spleen cells and thymus cells, respectively. In i.t. transfer experiments, the number of cells required for generating donor-type T cells was much lower than that in i.v. transfer experiments, although the ratio in 50% positive values between i.v. and i.t. transfers differed among cell sources. In i.t. transfers, the 50% positive value of bone marrow cells was five times, 400 times, and 500 times higher than that of fetal liver cells, spleen cells, and thymus cells, respectively. Our previous finding that stem cells are enriched in the spleens of mice which were whole body-irradiated and marrow-reconstituted 7 days earlier was confirmed also by the present limiting dilution assay carried out in i.v. as well as i.t. transfers.

Animals↗
PubMed1986

Age-related change in the potential of bone marrow cells to repopulate the thymus and splenic T cells in mice.

Bone marrow chimeras were produced between various combinations of young and old mice using either C57BL/6 mice only or a combination of C57BL/6 and B10.Thy-1.1 mice. The wet weight of the thymus and the number of thymocytes and splenic T cells of donor origin were assessed at appropriate intervals after the bone marrow transplantation. It was revealed that the old bone marrow was inferior to young in terms of the capacity to repopulate the thymus and splenic T cells. Moreover, some age-related qualitative changes appeared to occur in the thymocyte progenitors, as the composition of Lyt phenotype of donor-type T cells in the spleen was different between chimeras produced with young bone marrow and those with old.

Aging↗
PubMed1986

Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras.

The regeneration and persistence of host- and donor-derived T cells were examined in the thymus as well as the spleen of mouse radiation bone marrow chimeras of two semiallogeneic combinations (F1----P, P----F1) with different Thy-1 markers on T cells of donor and host origins. An unexpectedly large number of host-type T cells were recovered from the spleens of F1----P chimeras, amounting to as high as 45 and 25% of total T cells at 6 and 14 weeks after bone marrow transplantation (BMT), respectively. To the contrary, the residual host-type T cells in the spleens of P----F1 chimeras disappeared quickly, resulting in less than 0.1% of total T cells at 6 weeks after BMT. It was also revealed that the number of host-type T cells in the spleens of F1----P chimeras decreased in proportion to increase of radiation dose given to the recipients.

Animals↗
PubMed1985

Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study.

Immunohistochemical studies were made on the regeneration of T cells of host- and donor-type in the thymus and spleen of radiation bone marrow chimeras by using B10- and B10.BR-Thy-1 congenic mice. Both the thymic cortex and the medulla were first repopulated with thymocytes of irradiated host origin, restoring the normal histologic appearance by days 11 to 14, regardless of the H-2 compatibility between the donor and the host. In Thy-1 congenic chimeras, thymocytes of donor bone marrow origin, less than 100 cells in one thymic lobe, were first recognized at day 7, when the thymus involuted to the smallest size after the irradiation. The thymocytes of donor-type then proliferated exponentially, showing a slightly faster rate when higher doses of bone marrow cells were used for reconstitution, reaching a level of 100 million by day 17 and completely replacing the cortical thymocytes of host origin by day 21. The replacement of cortical thymocytes started from the subcapsular layer in a sporadic manner. The replacement of medullary thymocytes from host- to donor-type occurred gradually between days 21 and 35, after the replacement in the cortex was completed. In the spleen, about 1 million survived cells were recovered at day 3 after the irradiation, and approximately 60% of them were shown to be host-type T cells that were observed in the white pulp areas. The host-type T cells in the spleen increased gradually after day 10, due to the influx of host-type T cells from the regenerating thymus. Thus a pronounced increase of T cells of host-type was immunohistochemically observed in the splenic white pulp between days 21 and 28, when thymocytes of host-type were present mainly in the thymic medulla. These host-type T cells were shown to persist in the spleen for a long time, as long as 420 days after the treatment. Phenotypically, they were predominantly Lyt-1+2+ when examined at day 28, but 5 mo later, they were about 50% Lyt-1+2+ and 50% Lyt-1+2-. Donor-type T cells in the spleen began to appear at about day 14 in chimeras that were transplanted with a larger dose of bone marrow cells, whereas this was slightly delayed in those grafted with a smaller dose of bone marrow cells, starting at about day 28.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗