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Biomedical subjects

T Hamaoka

Publications and source records attributed to T Hamaoka.

At least 325 records · Page 18Linked to original sources
PubMed1982

Selective suppression of host T cell and macrophage activities during 7,12-dimethylbenz[a]anthracene-induced carcinogenesis.

The cellular mechanism of immunosuppression induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied by using both in vivo and in vitro assay systems. When the effect of DMBA on antibody responses was studied by the use of an adoptive cell transfer system of primed cells with second antigen in X-irradiated recipient mice, the development of both hapten-primed B cells and carrier-primed helper T cells induced by thymus dependent hapten-carrier conjugate was found to be markedly suppressed in DMBA-treated mice. When the B cell activity in DMBA-treated mice was directly assessed using thymus-independent hapten-carrier conjugate, anti-hapten antibody response was not suppressed at all. Since the development of hapten-primed B cells to thymus-dependent carrier requires the presence of carrier-primed helper T cells, DMBA treatment seems to affect primarily T cells but not B cells, and the suppression of development of hapten-primed B cells may be a secondary phenomenon induced by the suppressed helper T cell activities. Since the development of helper T cell activities requires antigen presentation by macrophages, it was determined which type of T cells or macrophages was the primary target of DMBA-induced immunosuppression. Antigen-primed T cells from DMBA-treated mice did not proliferate as well on stimulation with secondary antigen in vitro. Furthermore, antigen-pulsed macrophages from DMBA-treated mice did not fully activate T cells from normal mice. Thus, the primary target of DMBA-induced immunosuppression was considered to be on antigen-presenting macrophages rather than on T cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

The restoration of suppressed T cell activities induced by 7,12-dimethylbenz[a]anthracene with an anti-tumor immunomodulator, BCG-cell wall skeleton.

The restoring effect of Bacille de Calmette et Guérin (BCG)-cell wall skeleton (CWS) on the suppressed T cell reactivities in mice treated with 7,12-dimethylbenz[a]anthracene (DMBA) was studied using a system involving the induction of hapten-reactive cytotoxic T cells and mixed lymphocyte reaction in vitro. When the mice were treated with DMBA, the reactivity of lymphoid cells to generate cytotoxic T cells and proliferative T cell responses against allogeneic spleen cells was markedly suppressed. When BCG-CWS was administered to mice by intravenous injection before and after the treatment with DMBA, these depressed T cell functions reverted completely to the normal level. However, the restoration of the immune functions by BCG-CWS varied depending on the strain of mice. Namely, the reactivity of C57BL/6 mice was restored by BCG-CWS, whereas that of C3H/He mice was not. This strain difference correlates very well with the strain difference in effectiveness of the prevention of the DMBA-induced tumorigenesis by BCG-CWS. The possible relation between the restoration of T cell reactivities by BCG-CWS and prevention of tumorigenesis by BCG-CWS is discussed in the context of the role of host immune surveillance in the regulation of tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

[Lymphokines].

Lymphokines are defined as nonimmunoglobulin secretory products of activated lymphocytes with a wide range of potent physiological effects on inflammation and immune responses. In this review, we summarized the recent development in lymphokine researches, including biochemical and immunological approaches. An increasing number of assay methods enabled us to detect various lymphokine activities released in the culture medium of lectin activated lymphoid cells. However, some of the results in a number of independent studies about lymphokines were rather complicated for precise interpretation, since the lymphoid cell-culture medium comprises a mixture of very heterogeneous lymphokines molecules. This problem has now been overcome by generating hybridomas producing rather homogeneous lymphokine. By utilizing such relatively homogeneous lymphokines, we analyzed the mechanism of cytoxic T lymphocyte (CTL) generation, and discussed a possibility for utilization of this approach to the future antitumor immunotherapy.

Animals↗
PubMed1982

Acceptor site(s) for T cell-replacing factor (TRF) on B lymphocytes. II. Activation of B cells by cross-linkage or aggregation of the TRF acceptor molecule.

An in vitro experimental system was established to demonstrate the TRF-substituting activity of an alloantiserum raised in TRF low-responder (DBA2/2Ha x BALB/c)(DC)F, male mice against TRF high-responder parental BALB/c B cells. The TRF substituting activity of the antiserum was apparent in that anti-Thy-1 plus C-treated, DNP-primed B cells from TRF high-responder mice were effectively stimulated, whereas B cells from TRF low-responder DBA/2Ha mice were not, as evidenced by the induction of secondary anti-DNP IgG PFC responses. The specificity of the reaction of the antibody with a component present on the TRF high-responder B cells was also substantiated by the fact that antibody activity was virtually eliminated by absorption with B cells from various TRF high-responder mice but not by TRF low-responder DBA/2Ha B cells. The IgG fraction of antiserum and the F(ab')2 and Fab' fragments of the antibody, which possess a comparable reactivity in regard to the TRF acceptor site(s), were prepared, and analysis of the B cell-triggering mechanism by the antibody was carried out. The results revealed that both the IgG fraction and F(ab')2 fragment, but not the monovalent Fab' fragment, demonstrated effective TRF-substituting activity, indicating that cross-linkage or aggregation of the TRF acceptor site(s) may give rise to differentiation signals to the B cells.

Animals↗
PubMed1982

Expression of differentiation antigens cross-reactive with Ly-6.2 alloantigens on MM102 mouse mammary tumor cells.

The present study was carried out to investigate the immunobiological nature of alien antigens which appear as tumor-associated transplantation antigens (TATA) on MM102 mammary tumor cells. Anti-MM102 tumor-specific anti-serum obtained was used for examining the expression of antigens cross-reactive with TATA of MM102 tumor on lymphoid cells from allogeneic mice. The results demonstrate that this antiserum exhibited an appreciable degree of reactivity against C57BL/6, but not against C3H/He or BALB/c spleen cells. Further analysis revealed that thymocytes and bone marrow cells were marginally susceptible to treatment with anti-MM102 antibody plus complement. In contrast, portions of peripheral T and B lymphocytes were found to exhibit such cross-reactive antigens. It was also demonstrated that the strain distribution of expression of MM-TATA-cross-reactive antigens was completely correlated with that of Ly-6.2 alloantigens. Moreover, anti Ly-6.2 monoclonal antibody lysed MM102 tumor cells in the presence of rabbit complement. These results indicate that TATA of MM102 tumor cells are cross-reactive with differentiation antigens which develop on allogeneic lymphoid cells and are closely related to Ly-6.2 alloantigens.

Animals↗
PubMed1981

A novel immunization procedure for production of anti-cholecystokinin-specific antiserum of low cross-reactivity.

An anti-cholecystokinin octapeptide (CCK-8) antibody without cross-reactivity with pentagastrin, whose amino acid sequence is identical with the carboxy-terminal portion of CCK-8, was produced by immunization with CCK-8-keyhole limpet hemocyanin and injection of a conjugate of pentagastrin and a copolymer of D-glutamic acid and D-lysine to inhibit production of antibody cross-reacting with pentagastrin.

Animals↗
PubMed1981

X-linked recessive inheritance of a defective responsiveness to T-cell-replacing factor in DBA/2Ha mice.

TRF responsivity of B-cells from an F1 hybrid of the low-responder strain DBA/2Ha (female) and the high-responder strain BALB/c (male), or their reciprocal F1 hybrid (BALB/c (female) X DBA/2Ha (male)), was analyzed. In every case the B-cells from all of the male mice of the (DBA/2Ha X BALB/c) (DC)F1 hybrid were incapable of responding to TRF, whereas B-cells from female mice of the same litter responded to TRF. In contrast, B-cells from both male and female (BALB/c X DBA/2Ha) (CD)F1 mice were able tp respond to TRF, strongly suggesting that the responsivity of B-cells to TRF is controlled by the X-chromosome of the high-response animals. To substantiate further the evidence for a X-linked B-cell defect in DBA/2Ha mice, we analyzed TRF responsivity of B-cells from back-cross (DCF1 (female) X DBA/2Ha (male)) progeny and from F2 (DCF1 X DCF1) progeny, respectively. In both crosses we observed segregation of TRF responsivity into high-responder and low-responder groups in a nearly 1:1 ratio. These findings further indicated that a major component involved in the regulation of TRF responsivity is carried on the X-chromosome. This component is defective in DBA/2Ha mice, the defect being inherited in a recessive manner.

Animals↗
PubMed1981

Immunological properties of Fc receptor on lymphocytes. 9. Functional analysis of FcR gamma+ and FcR gamma- lymphocytes in IgE antibody responses.

The present study was undertaken to clarify the function of FcR gamma+ and FcR gamma- lymphocytes in anti-DNP IgE antibody responses. The helper activity was observed predominantly in FcR gamma- T cells, but poorly in FcR gamma+ T cells, as in the case of IgG antibody responses, indicating that the absence of FcR gamma on T cell surface is a common surface characteristic to helper T cells, and that there is no close relationship between the determination of class specificity of Ig and T cell subsets divided by the presence or absence of FcR gamma. Furthermore, IgE antibody responses were more dependent upon helper T cells than IgG antibody responses. The data presented in this paper also demonstrated that the precursors of anti-DNP IgE antibody-forming cells were equally contained in both FcR gamma+ and FcR gamma- B cells, when they were transferred into recipients with helper T cells. This is a striking contrast to IgM/IgG antibody responses, in which only FcR gamma- B cells could differentiate into antibody-forming cells. Moreover, the precursor activity of FcR gamma+ and FcR gamma- B cells for IgE antibody-forming cells was not affected by the treatment of cells with suppressive B cell factor released from FcR gamma+ B cells after binding of antigen-antibody (IgG) complexes and known to suppress the proliferation of FcR gamma- IgM/IgG antibody-forming cell precursors. Thus, IgE B cells seem to be more heterogeneous than IgM/IgG B cells with respect to the FcR gamma marker and insensitive to the regulatory effect of FcR gamma+ B cells. IgE B cells are regulated differently from IgG B cells in B-B cell interactions.

Animals↗
PubMed1981

Detection of the dominant expression of the TEPC-15 idiotypic determinant(s) on phosphorylcholine-specific suppressor T lymphocytes in vitro.

Phosphorylcholine-(PC) specific suppressor T lymphocytes, induced by immunization with PC-coupled syngeneic spleen cells and capable of suppressing antibody production in an in vitro system, were successfully obtained by removal of a PC-nonspecific, i.e., diazo-phenylstructure-directed, suppressor cell population using an immunoadsorbent column coupling an unrelated hapten with a diazo phenyl structure such as azobenzene arsonate (ABA). Column-purified PC-specific suppressor T cell activity was completely abrogated by treatment of the cells with anti-TEPC-15 (T-15) anti-idiotypic antibody and complement, or by the continuous presence of that antibody in the culture, whereas nonpurified suppressor cell activity was resistant to such treatment. Thus, the column-purified PC-specific suppressor T lymphocytes in BALB/c mice have a very homogeneous T-15 idiotypic determinant(s) on their functional receptors for antigen similar to those present on PC-specific antibody and/or B lymphocytes. Because of these results, we envision the growing importance of analysis of the fine specificity of the idiotype repertoire of T lymphocytes after purification of a hapten-specific population.

Animals↗
PubMed1981

The mechanism of specific suppression in effector T cell clones against tumor-associated transplantation antigens.

The present study investigates the fate of effector T cell population against tumor-associated transplantation antigens (TATA) of X5563 plasmacytoma in syngeneic mice rendered specifically unresponsive to the TATA. In this tumor system T cell-mediated tumor-specific immunity was induced by intradermal inoculation of viable tumor cells followed by the surgical resection of the tumor (immunization procedure). The intravenous (iv) presensitization of syngeneic hosts with X-irradiated tumor cells abolished the capability of those hosts to develop the tumor-specific immunity after the above appropriate immunization procedure. Spleen cells from the pretreated mice which subsequently received the immunization procedure could not regain the tumor-neutralizing activity after enzymatic treatment with papain. Moreover, lymphoid cells from the pretreated mice could not be stimulated by the immunization procedure even after proteolytic treatment with papain or trypsin, followed by transfer into other recipient mice free of the serum suppressive factor(s). On the other hand, such enzyme treatment was capable of preventing the tolerance induction of dinitrophenyl (DNP)-primed B cells after in vitro pulsing with DNP-D-GL (copolymer of D-glutamic acid and D-lysine) for 2 hr, suggesting that the enzymatic treatment used here was adequate to remove the blocked receptor and any tolerogen. These results suggest that in X5563 plasmacytoma system, the above specific unresponsiveness induced by the iv presensitization with TATA is due to the irreversible inhibition or deletion of effector T cell clones rather than mere effector cell blockade.

Animals↗
PubMed1981

Inhibitory effect of Propionibacterium acnes-activated macrophages on the tumor metastasis enhanced by tumor-specific immunosuppression.

The present study deals with the mechanism by which Propionibacterium acnes (P. acnes) prevents metastasis formation in C3H/He mice which had been rendered tolerant to tumor-associated transplantation antigen (TATA) of syngeneic X5563 plasmacytoma by intravenous (iv) inoculation of 10(6) X-irradiated tumor cells 3 times at 4-day intervals. In these TATA-tolerant mice, systemic metastasis formation was enhanced after intradermal (id) implantation of viable tumor cells, even if the tumor was resected surgically 7 days thereafter. Administration of P. acnes to these TATA-tolerance mice induced appreciable prevention of the metastasis formation. When we passively transferred P. acnes-activated peritoneal exudate cells (PECs) instead of P. acnes into TATA-tolerant mice, successful prevention to metastasis was also observed, irrespective of whether they were derived from TATA-tolerant mice or from normal naive mice. In both in vivo and in vitro assay systems, the P. acnes-activated PECs from TATA-tolerant mice as well as from normal naive mice showed potent anti-tumor activity. In the in vitro assay, anti-tumor effector cells in P. acnes-activated PECs were found to reside in a plastic adherent population resistant to treatment with anti-Thy-1 plus complement. These results are consistent with the view that effector cells for the prevention of metastasis are activated macrophages. The significance of these findings is discussed in relation to the possibility of the future application of an immunomodulator which activates macrophages to prevent metastasis.

Animals↗