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T Sado

Publications and source records attributed to T Sado.

At least 91 records · Page 5Linked to original sources
PubMed1985

Cellular events during radiation-induced thymic leukemogenesis in mice: abnormal T cell differentiation in the thymus and defect of thymocyte precursors in the bone marrow after split-dose irradiation.

Cellular events during the development of thymic lymphomas in young B10.BR mice given leukemogenic split-dose irradiation were studied by examining the differentiation of functional T lymphocyte precursors in the regenerating thymus. It was found that leukemogenic radiation treatment resulted in a sustained depression of the level of thymic cytotoxic T lymphocyte precursors (CTLp) and of mixed lymphocyte reactivity of thymus cells when assessed between 1 and 4 mo after irradiation, in spite of the fact that the total number of thymocytes was restored to the normal level within 2 mo and continued to increase thereafter. In vitro mixing studies of normal thymocytes with thymus cells from split-dose irradiated mice provided no evidence for active suppression as a mechanism for this depressed activity. The ability of bone marrow cells from split-dose irradiated mice to regenerate the thymus and to differentiate into functional CTLp was examined by use of supralethally irradiated Thy-1 congenic recipients. Reconstitution of supralethally irradiated B10.BR Thy-1.2 mice with normal bone marrow from B10.BR Thy-1.1 mice resulted in the complete repopulation of host-thymus with donor-derived cells when assessed at 4 wk after reconstitution. Lymphocytes from the regenerating thymus of these animals were shown to contain high levels of CTLp which were donor-derived. On the other hand, when the recipient mice were reconstituted with bone marrow cells from donor mice which had been split-dose irradiated 1 mo earlier, regeneration of the recipient thymus was severely depressed when assessed at 4 wk to 3 mo after reconstitution. Although variable but small numbers of donor-derived Thy-1+ cells were detected, CTL activity for alloantigen could not be induced in these donor-derived cells. The results suggest that T cell precursors derived from split-dose irradiated donor mice were unable to undergo active proliferation and differentiation into functional CTLp. The significance of these findings on radiation-induced thymic leukemogenesis is discussed.

Animals↗
PubMed1985

Strain difference in the radiosensitivity of immunocompetent cells and its influence on the residual host-vs-graft reaction in lethally irradiated mice grafted with semiallogeneic bone marrow.

A striking difference in radiosensitivity was noted between C3H/He (H-2k) and C57BL/6J (H-2b) strain mice when assessed by primary anti-SRBC PFC response of intact animals and primary cell-mediated lympholysis (CML) response of spleen cells to allogeneic cells in vitro, the C3H strain being more radioresistant. On the other hand, when C3H and B6 mice were exposed to 6.62 to 10.40 grays (Gy) of x-rays and then were transplanted with 2 X 10(6) bone marrow cells from B6C3F1 (H-2b/k) donor mice within 3 hr or at 24 hr after radiation exposure, the early mortality caused by residual host-vs-graft (HVG) reaction was much higher when C3H mice were used as recipients. Furthermore, the proportion of surviving animals manifesting host-type lymphohemopoiesis, i.e., host-type revertants, was much higher in B6C3F1 to C3H than in B6C3F1 to B6 combination. Spleen cells from such host-type revertants manifested strong anti-donor reactivity when assessed by mixed lymphocyte reaction (MLR) and/or CML in vitro. Increase of radiation doses to the recipients to 10.40 Gy resulted in 100% survival and 100% donor-type lymphohemopoiesis in both groups of chimeras. These results indicate strongly that a genetic difference in radiosensitivity of immune system of the recipients can greatly influence the magnitude of residual HVG reactions observed in hybrid to parental strain bone marrow transplantation in mice.

Animals↗
PubMed1985

Two subpopulations of stem cells for T cell lineage.

An assay system for the stem cell that colonizes the thymus and differentiates into T cells was developed, and by using this assay system the existence of two subpopulations of stem cells for T cell lineage was clarified. Part-body-shielded and 900-R-irradiated C57BL/6 (H-2b, Thy-1.2) recipient mice, which do not require the transfer of pluripotent stem cells for their survival, were transferred with cells from B10 X Thy-1.1 (H-2b, Thy-1.1) donor mice. The reconstitution of the recipient's thymus lymphocytes was accomplished by stem cells in the donor cells and those spared in the shielded portion of the recipient that competitively colonize the thymus. Thus, the stem cell activity of donor cells can be evaluated by determining the proportion of donor-type (Thy-1.1+) cells in the recipient's thymus. Bone marrow cells were the most potent source of stem cells, the generation of donor-derived T cells being observed in two out of 14 recipients transferred with as few as 1.5 X 10(4) cells. The stem cell activity of spleen cells was estimated to be about 1% of that of bone marrow cells, and no activity was found in thymus cells. By contrast, when the stem cell activity was compared between spleen and bone marrow cells of whole-body-irradiated (800 R) C57BL/6 mice reconstituted with B10 X Thy-1.1 bone marrow cells by assaying in part-body-shielded and irradiated C57BL/6 mice, the activity of these two organs showed quite a different time course of development. Spleen cells showed a markedly high level of activity 7 days after the reconstitution, followed by a decline, whereas the activity of bone marrow cells was very low on day 7 and increased crosswise. The results strongly suggest that the stem cells for T cell lineage in the bone marrow comprise at least two subpopulations, spleen-seeking and bone marrow-seeking cells. Such patterns of compartmentalization of stem cells in the spleen and bone marrow of irradiated recipients completely conform to the general scheme of the relationship between restricted stem cells and less mature stem cells, including pluripotent stem cells, which became evident in other systems such as in the differentiation of spleen colony-forming cells or of stem cells for B cell lineage.

Animals↗
PubMed1984

Radiation effects on regeneration and T-cell-inducing function of the thymus.

Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunological functions was observed even by local irradiation of 2000 R.

Aging↗
PubMed1984

Anti-viral immune response of allogeneic irradiation bone marrow chimeras: cytotoxic T cell responsiveness depends upon H-2 combination and infectious agent.

Allogeneic irradiation bone marrow chimeras C57BL/10 (H-2b) leads to B10.BR (H-2k) and B10.BR (H-2k) leads to C57BL/10 (H-2b) were raised under specific pathogen-free (SPF) conditions; they survived very well and were healthy under SPF for 3-4 months and subsequently, under conventional housing conditions, for 1 to 8 months. Their immune response against third-party alloantigens was comparable with that of controls. Anti-vaccinia virus responses were very low when compared with syngeneic control chimeras or unmanipulated control animals; if anti-vaccinia virus cytotoxic T cell reactivity was measurable, it was specific for the bone marrow donor, rather than the recipient thymic H-2 type. In contrast, the anti-LCMV (lymphocytic-choriomeningitis virus) response was excellent and comparable to that in controls for B10.BR (H-2k) leads to C57BL/10 (H-2b) chimeras, but was completely absent for C57BL/10 (H-2b) leads to 10.BR (H-2k) chimeras. LCMV-specific cytotoxic effector T cells from B10.BR leads to C57BL/10 chimeras were restricted entirely to recipient H-2b. In contrast to the asymmetric cytotoxic T cell response, both types of chimeras developed good primary footpad swelling reactions after local infection, which arose somewhat slower with LCMV than in control of chimeras. The capacity to control infection by Listeria monocytogenes was excellent for all controls and B10.BR leads to C57BL/10 chimeras but apparently absent in C57BL/10 leads to B10.BR chimeras. Differentiation of T cell restriction specificity for thymic H-2 is apparently most efficient, but it remains unclear whether the observed asymmetry reflects exaggerated immune response regulation in H-2-incompatible stem cell-thymus chimeras or differential cross-reactivities between restricting transplantation antigens.

Animals↗
PubMed1984

H-2 restriction specificity of T cells from H-2 incompatible radiation bone marrow chimeras: further evidence for the absence of crucial influence of the host/thymus environment on the generation of H-2 restricted TNP-specific T lymphocyte precursors.

Experiments were conducted to answer the questions related to (a) the role played by the antigen-presenting cells (APCs) present within the thymus and (b) the effect of radiation dose to the recipients on the H-2 restriction profile of TNP-specific cytotoxic T lymphocyte precursors (CTLP) recovered from spleens and/or thymuses of H-2 incompatible radiation bone marrow chimeras (BMC). The H-2 restriction profile of intrathymically differentiating TNP-specific CTLPs was also analyzed in order to test an argument that donor-H-2 restricted CTLP detected in spleens of H-2 incompatible BMC were due to the extrathymically differentiated T cells under the influence of donor-derived lymphoreticular cells. The results indicated the following: (i) splenic T cells from B10(H-2b) leads to (B10(H-2b) leads to B10.BR(H-2k)) chimeras, which were constructed by irradiating primary B10 leads to B10.BR chimeras with 1100 R and reconstituting them with donor-type (B10) bone marrow cells as long as 8 months after their construction, manifested restriction specificities for both donor- and host-type H-2, (ii) splenic T cells from two types of (B10 X B10.BR)F1 leads to B10 chimeras which were reconstituted after exposure of the recipients with either 900 or 1100 R with donor-type bone marrow cells generated both donor- and host-H-2 restricted TNP-specific cytotoxic T cells, and (iii) the TNP-specific CTLPs present in the regenerating thymuses of B10.BR leads to B10 and (B10 X B10.BR)F1 leads to B10 chimeras 4 weeks after their construction were also shown to manifest both donor- and host-H-2 restriction specificities. The significance of these findings on the H-2 restriction profile of CTLP generated in BMCs is discussed.

Animals↗
PubMed1983

Reconfirmation of indirect induction of radiogenic lymphomas using thymectomized, irradiated B10 mice grafted with neonatal thymuses from Thy 1 congenic donors.

An experiment was conducted to reexamine earlier observations that lymphomas could develop from lymphocytes present in nonirradiated thymuses grafted into thymectomized, fractionally (170 R, 4 doses) irradiated mice by using B10. Thy 1 congenic donor-host combinations. The results indicated that: (a) 37 of 91 thymectomized, fractionally irradiated B10. Thy 1.2 mice which were grafted s.c. with 7-day-old thymuses from B10. Thy 1.1 donor mice had developed frank lymphomas between 90 and 270 days after thymus grafting; (b) 28 of 37 lymphomas developed in this group were typed individually with respect to Thy 1 alloantigens by the cytotoxicity assay using monoclonal anti-Thy 1.1 (T-11-D7) and anti-Thy 1.2 (F7D5) antibodies plus complement. It was shown that 21 thymic lymphomas (75%) had originated from lymphocytes of the nonirradiated thymus grafts and 5 tumors (17.9%) from cells of the irradiated hosts; 2 thymic lymphomas (7.1%) manifested no Thy 1 antigens; (c) lymphoma cells originated from both nonirradiated thymus grafts and irradiated hosts possessed chromosome abnormalities, which were mainly numerical changes of some chromosomes or polyploidizations.

Animals↗
PubMed1983

Chromosomal aberrations observed in 52 mouse myeloid leukemias.

Chromosomes of 52 cases of mouse myeloid leukemia were examined. There were 5 myeloblastic leukemias, 22 granulocytic leukemias, 17 myelomonocytic leukemias, and 8 monocytic leukemias. Fifty cases were radiation induced and the other 2 were nonirradiated. Each case had leukemic cells with 1 to 10 marker chromosomes. Partially deleted No. 2 chromosomes appeared in 49 cases, including 2 nonirradiated cases. These deleted No. 2 chromosomes were varied in size, and they were classified into 7 types according to morphological features. There was no type-dependent difference in histological or cytological features among the 7 types. It was found that the chromosomal segment lying between Regions 2C and 2D was commonly missing from all of the deleted No. 2 chromosomes. In addition to such No. 2 chromosomes, an anomaly in chromosome 6 was observed in 16 cases, of which 12 cases were granulocytic leukemia. The abnormalities of chromosomes 3 and 9 were next most frequent, appearing in 14 cases each. Besides such structural anomalies, numerical changes involving the Y chromosome (33 cases), chromosome 6(6 cases), and chromosome 15 (4 cases) were also found. Characteristics of the karyotypes of the mouse myeloid leukemia in comparison with other leukemias were noted. The significance of the specific segments of the chromosomes which were commonly missing or trisomic in the karyotypes of neoplasias in mice, rats and humans was discussed. It was suggested that the genesis of myeloid leukemia was greatly influenced by the genetic information on chromosome 2 in mice.

Animals↗
PubMed1982

Evidence for involvement of mast cells in tumor suppression in mice.

Mast cell-deficient W/Wv mice had an increased tumor incidence after subcutaneous treatment with 3-methylcholanthrene, compared with that in normal congenic mice treated in the same way. This increased tumor incidence was suppressed to the normal level when the carcinogen was given after the mast cell deficiency had been overcome by transplantation of bone marrow cells from normal congenic mice. The W/Wv mice, however, were not defective in natural killer and T-cell-mediated cytotoxic activities. These results support the hypothesis that mast cells are involved in tumor suppression.

Animals↗
PubMed1981

Regulation of primary antibody response in mice by two types of suppressor cells resistant to anti-thy-1 serum treatment.

The anti-SRBC antibody response of normal young adult mice (about 3 months old) was specifically suppressed, when the spleen cells derived from the syngeneic donor mice that had been previously primed with a high dose of SRBC were adoptively transferred at the time of antigenic challenge. The suppression was antigen-specific and was mediated by a fraction of the immune spleen cells which appeared to belong to either B cells or their progeny antibody-forming cells. The differences were observed in the properties of the suppressor cells in terms of the period after the priming and the radiosensitivity; i.e., immune spleen cells taken from the mice which had been immunized with SRBC 5 days earlier were able to suppress only 19S PFC, whereas those taken from the mice which had been immunized 14 days earlier were able to suppress both the 19S and 7S PFC responses, and the former cells were susceptible to 400 R X-rays, but not the latter. These two types of suppressor cells appeared to play an important role in the regulation of the sequential change of 19S and 7S antibodies during the primary immune response.

Animals↗
PubMed1979

Partial deletion of chromosome No. 2 in myelocytic leukemias of irradiated C3H/He and RFM mice.

Chromosomes of mouse myelocytic leukemias that developed in 7 irradiated mice, 3 C3H/He males, 1 RFM female, and 3 RFM males were analyzed with chromosome-banding techniques. Chromosomes No. 2 were partially deleted in 6 of the 7 mice. Although the deleted No. 2 chromosomes varied in size in the 6 mice, one common characteristic was noted in all these deletions: A segment lying between a certain band in the region 2C and a band in the region 2E, including the whole region 2D, was missing. Another consistent abnormality was an addition or a loss of the Y-chromosomes in the fraction of cells in all 6 males. In addition to these consistent abnormalities, various chromosomes had structural abnormalities. The RFM female, which did not have the abnormal No. 2 chromosome, had abnormalities in chromosomes No. 3, 4, 11, 12 and 15 and in the X-chromosome. Of the 20 chromosome pairs, only such chromosomes as No. 1, 5, 8, 14, 17, and 19 and the Y-chromosome did not have the structural abnormalities. The possible role of the partial deletion of the No. 2 chromosome was considered in relation to the development of mouse myeloid leukemias.

Animals↗
PubMed1979

Absence of correlation between T-lymphocyte activity and development of carcinogen-induced skin tumor in mice.

Splenic lymphocytes obtained from female ICR/JCL mice, which had received combined radiation and chemical treatment for induction of skin tumors on their back skin, were tested for their ability to undergo proliferative response to non-specific mitogens as well as to allogeneic lymphocytes in vitro during 18 months after carcinogenic treatment. The treated mice, 168 in all, were divided into three groups: (a) 53 mice with no tumor, (b) 30 mice with skin papilloma, and (c) 85 mice with malignant skin tumor. Control mice, 39 in all, received no treatment. The local carcinogenic treatments used in this study induced a relatively long-lasting suppression of T-cell activities as detected by proliferative response to mitogens. Nevertheless, there was no significant difference in T-cell activities among the three groups of mice that developed (a) no tumor, (b) skin papilloma, or (c) malignant skin tumor. The results obtained with proliferative response to allogeneic lymphocytes were essentially similar. A preliminary study on the induction of cytotoxic T cells from splenic lymphocytes against allogeneic target cells in vitro also indicated that mice which developed tumors were not necessarily the ones which manifested reduced cytotoxic T-cell activity. These results suggest that reduced T-cell function was not a direct cause or not even a prerequisite for development of skin tumors in ICR mice.

Age Factors↗
PubMed1978

Early decline of thymic effect on T cell differentiation.

Thymic lobes of B6C3F1 mice ranging in age from 1 day to 11 weeks were implanted under the kidney capsule of T cell deprived syngeneic young adult TXB mice, and the capacity of the thymus grafts to influence the maturation of T cells was assessed at 6 and 12 weeks after the implantation in terms of (a) regenerative activities of the grafted thymus, (2) splenic T cell dependent anti-SRBC response, and (c) mitogenic reactivity of spleen and lymph node cells to T cell specific mitogens. The results revealed that: (1) thymic tissues from 1 week old donors were most efficient in restoring the immune potential of adult TXB mice; (2) a decline in mitogenic reactivities of spleen and lymph node cells was observed in recipients of thymus grafts from donors of 1 month and older; and a decline of splenic helper T cell function was observed in recipients of thymus grafts from 11 weeks old donors. The significance of this early decline in the thymic effect on T cell differentiation is discussed.

Aging↗