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Biomedical subjects

T Hamaoka

Publications and source records attributed to T Hamaoka.

At least 361 records · Page 20Linked to original sources
PubMed1978

Selective expression of paternal human major histocompatibility antigens on the surface of hydatidiform mole cells.

The typing of human major histocompatibility antigens (HLA) of two cases of invasive hydatidiform mole showed that the fibroblast-like cells as well as trophoblasts from the mole selectively expressed paternal HLA haplotype specificity but not maternal HLA on the surface. This result was completely in agreement with the notion of androgenetic origin of hydatidiform mole from the aspects of HLA specificity. Immunological implication of this finding and development of chorionic tumor were discussed in the light of fetomaternal relationship and host immune surveillance against the tumor.

Epitopes↗
PubMed1977

Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. I. Detection and characterization of hapten-reactive suppressor T-cell activity in mice immunized with hapten-isologous protein conjugate.

Helper and suppressor T-cell activities were detected simultaneously in the spleen cells of mice immunized with para-azobenzoate (PAB)-mouse gammaglobulin (MGG). Dinitrophenyl (DNP)-specific B cells were raised by immunization with DNP-keyhole limpet hemocyanin (KLH) and used as the indicator B-cell population. The helper and suppressor T-cell activities were determined after adoptively transferring spleen cells from PAB-MGG- primed donors and DNP-KLH-primed donors into X-irradiated recipients. Stimulation of these recipients with DNP-MGG-PAB detected helper T-cell activity, which was measured in terms of increased anti-DNP antibody responses of DNP-KLH-primed cells over these responses in the presence of unprimed cells. On the other hand, when DNP-KLH-primed cells were stimulated with DNP-KLH-PAB in the presence of PAB-MGG-primed cells, anti-DNP antibody responses were substantially lower than in unprimed normal cells. This suppressor cell population was (a) hapten-reactive, (b) present in B-cell-depleted spleen cells, (c) Thy-1 positive, (d) detectable earlier than the helper T-cell activities after priming (e) more radiosensitive than helper cells, and (f) found in the spleen but not the lymph nodes in contrast to helper T cells. These data indicate that these suppressor T cells are distinct from the helper T cells. PAB-reactive T cells clearly suppressed the antibody response by inhibiting KLH-reactive helper T-cell functions. The hapten-reactive T-lymphocyte system described here should be useful for analyzing and manipulating the immune response and for studying regulatory interactions of helper and suppressor T cells in the induction of antibody responses.

Animals↗
PubMed1977

Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development.

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

Animals↗
PubMed1977

Inhibitory effect of tumor-bearing state on the generation of in vivo protective immune T cells in a syngeneic murine tumor system.

Tumor-specific immunity mediated by thymus-derived lymphocytes (T cells) was established in C3H/He mice against syngeneic X5563 plasmacytoma. Splenic T cells from mice, which exhibited resistance to tumor challenge, revealed a potent in vivo tumor-neutralizing activity as well as in vitro cytotoxicity. In contrast, spleen cells from mice 7 days after tumor cell inoculation (7-day tumor-bearing mice) exhibited no protective activity when assayed by in vivo tumor-neutralization test, whereas these cells exhibited almost comparable in vitro cytotoxic activity to that from the tumor-resistant mice. Any suppressor cell activity was not detected in 7-day tumor-bearing animals. While a slight in vivo protective activity was observed in the spleen cells from 14-day tumor-bearing mice, this activity was still significantly weaker than that of spleen cells from mice similarly inoculated with tumor 14 days before but whose tumor had been removed 7 days before the assay. The development of in vivo protective immunity in tumor-resected mice was suppressed by intravenous inoculation with 7000 R X-irradiated tumor cells. These results indicate that in vitro reactivity of immune T lymphocyte population is not always correlated with in vivo protective immunity, but there is a substantial decrease in in vivo immune capability of T cells from tumor-bearing animals, and that this suppression may be ascribed to the presence of a large amount of tumor-associated transplantation antigens rather than to suppressor cell activity.

Animals↗
PubMed1976

Selective inhibition of T lymphocyte repopulation of lymphoid organs as a mechanism of immunosuppression in tumor-bearing mice.

The mechanism of selective suppression of T-cell activity in Ehrlich tumor-bearing mice was investigated in an adoptive cell transfer system of secondary antibody responses to haptens. The induction of secondary antidinitrophenyl (DNP) antibody response after stimulation with DNP-homologous carrier (TD) of thymus-dependent DNP-carrier (TD)-primed spleen cells was markedly inhibited in tumor-bearing recipient mice, whereas the response to thymus independent DNP-carrier (TID) was intact as compared to that seen in normal recipients. However, if tumors were induced in the DNP-TD-primed donor mice and the spleen cells were assayed for responsiveness to DNP-TD in normal recipients, they generated a normal anti-hapten antibody response. After the DNP-TD-primed cells had been transferred into normal recipients and tumors had been induced in the recipients before DNP-TD-stimulation, the cells in tumor-bearers responded normally. These results indicate that the tumor-bearing state neither directly suppresses the responsiveness of primed cells nor interferes with the mechanism for antigen stimulation of primed cells. Direct measurement of recovery of transferred primed T and B cells from the spleen of tumor-bearing recipients revealed that the net recovery of T-cell activity markedly decreased, whereas the recovery of B cells in the spleens of tumor-bearing hosts was not affected or was even higher than the normal. Prevention of repopulation by T lymphocytes of lymphoid organs due to a postulated change in the microenvironment is suggested as a mechanism for the selective suppression of T-cell activity in Ehrlich tumor-bearing animals.

Animals↗
PubMed1976

Serum dependence of expression of the transformed phenotype: experiments with subline of mouse L fibroblasts adapted to growth in serum-free medium.

Characteristics of LSF cells grown in serum-containing and serum-free medium were compared. LSF is a subline of the L-strain of mouse transformed fibroblasts adapted to continuous growth is serum-free medium. Proliferation of LSF cells in monolayer on solid substratum was almost similar in serum-containing and in serum-free media. However, several other characters were found to be altered by the addition of serum to the serum-free medium: ability of cells to form colonies in semi-solid medium increased considerably; agglutinability of cells by Concanavalin A increased; uptake of 2-deoxy-D-glucose by the cells increased considerably; ability of cells to metabolize benzo (a) pyrene was inhibited; cell morphology was altered and, in particular, the cells became less spread on the substratum and density of microvilli on the cell surface increased. All these changes induced by serum were reversed by transfer of the cells back into serum-free medium. Thus, addition of serum increased the expression of a number of cellular traits characteristic of transformed phenotype, while in serum-free medium partial phenotypic reversion of transformation was observed. A possible role of serum in the expression of the transformed phenotype is discussed. It is pointed out that cell lines adapted to growth in serum-free medium provide an experimental system convenient for analysis of the effects of different serum components on the cell phenotype.

Animals↗
PubMed1976

Selective suppression of T-cell activity in tumor-bearing mice and its improvement by lentinan, a potent anti-tumor polysaccharide.

The cellular site of immunosuppression in Ehrlich tumor-bearing mice was analysed with particular reference to the T- and B-cell activities. The B-cell activity as measured by the anti-dinitrophenyl (DNP) antibody responses to DNP-thymus-independent carriers (TID) was not impaired in tumor-bearing mice as compared with normal mice, whereas the anti-DNP antibody response to DNP-thymus-dependent carriers (TD) and the development of helper T-cell activity to TD were markedly suppressed in tumor-bearing animals or mice pretreated with cell-free cancerous ascitic fluid. The selective suppression of T-cell response was not mediated by the generation of suppressor cell activity toward TD, which may depress the manifestation of developed helper T-cell activity. A marked suppression of T-cell response was observed when the animals were inoculated with tumor cells or injected with cancerous ascitic fluid prior to antigenic stimulation, but not when the animals were rendered tumor-bearing by such treatments after the immunization. The suppression of T-cell activity in both sarcoma 180 tumor-bearing mice and cell-free Ehrlich cancerous ascitic fluid-treated mice was prevented by treatment with lentinan, a potent anti-tumor polysaccharide. The applicability of this experimental system to the search for immunopotentiators relevant to tumor immunotherapy is discussed in the light of the preventive effect of lentinan on the suppression of T-cell response in tumor-bearing animals.

Animals↗
PubMed1976

Isolation of soluble immunosuppressive substance(s) from Ehrlich ascites tumor cell nuclei.

A potent immunosuppressive principle was isolated in a soluble form from the nuclei of Ehrlich ascites tumor cells. DNA-free preparation, obtained from the purified nuclei by homogenizing in 2M NaCl-5M urea solution and removing the dissociated DNA with LaCl3-precipitation, revealed strong activity to suppress the development of helper thymus-derived lymphocyte activity in mice. Moreover, almost all of the immunosuppressive activity originally found in the nuclear residue fraction after extraction with sodium citrate solution was recovered in 0.25 N HCl extract which mainly contains proteins. The nuclear components of tumor cells were also detected in the body fluid of tumor-bearing animals, as examined by the reactivity with a rabbit antiserum specific for some nuclear component of Ehrlich tumor cells. These results suggest that the immunosuppressive principle in the nuclei of Ehrlich tumor cells is a histone-like substance, and liberated into the body fluid from tumor cell nuclei in the tumor-bearing state.

Animals↗
PubMed1976

Preferential generation of killer or helper T-lymphocyte activity directed to the tumour-associated transplantation antigens.

Induction of killer and helper T-cell activities towards transplantation antigens of two tumour cell lines was analysed in the allogeneic and syngeneic host combinations. The lymphoid cells from C57BL/6 mice immunized with allogeneic viable or mitomycin C-treated X-5563 plasmacytoma cells derived from C3H/He mice revealed both killer and helper T-cell activities against alloantigens, whereas cells from mice immunized with tumour cells killed by a freezing and thawing procedure revealed predominantly helper T-cell activity. On the other hand, when C3H/He mice were immunized with viable syngeneic X-5563 plasmacytoma or MM102 mammary tumour cells, the former generated preferentially killer T-cell activity, whereas the latter induced predominantly helper T-cell activity against tumour-associated transplantation antigens. Thus, immunization with transplantation antigen(s) does not always induce both helper and killer T-cell activities in parallel, but a certain antigenic system induces predominantly one type of T-cell response, thus indicating that two distinct subsets of helper and killer T cells against the transplantation antigen(s) can be raised independently without an absolute requirement of collaboration between these different T-cells subsets.

Animals↗
PubMed1976

Proliferative response of T lymphocytes to allogeneic tumor without generation of killer T lymphocytes in the presence of Ehrlich ascites tumor fluid.

The presence of cell-free Ehrlich ascites tumor fluid in an appropriate concentration was shown to permit a proliferative response, strictly dependent on the presence of Thy-1-positive lymphocytes, to proceed when introduced on the initiation of mixed lymphocyte-tumor reaction of C57BL/6 lymphocytes and Mitomycin-C-treated C3H/He myeloma cells, while it clearly inhibited the development of cytotoxic killer T lymphocytes toward the priming allogeic tumor cells. The fluid had no effect, however, when added to normally primed spleen cells at the onset of cytotoxicity test. Further investigation of the mechanism in vitro by ascitic tumor fluid selectively suppresses the generation of killer T lymphocyte activity to allogeneic target cells may lead to a better understanding of the suppressed T-cell responses observed in Ehrlich tumor-bearing animals, and additionally, may provide an intriguing information about the interactions between the distinct T-cell subsets responsible for proliferative response and generation of killer T lymphocytes.

Animals↗