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T Hamaoka

Publications and source records attributed to T Hamaoka.

At least 289 records · Page 16Linked to original sources
PubMed1984

Both interleukin 2 and a second T cell-derived factor in EL-4 supernatant have activity as differentiation factors in IgM synthesis.

B cells cultured with anti-IgM, BSF-p1, and B15-TRF will differentiate into high rate IgM-synthesizing cells in the presence of supernatants from EL-4 cells that have been induced with phorbol myristate acetate. These supernatants contain two molecular species (EL-TRFs) that have differentiative activity. One co-migrates with interleukin 2 (IL-2) and its activity is blocked by antibody to the IL-2 receptor. Furthermore, molecularly cloned IL-2, at concentrations of 100 U/ml or more, expresses such EL-TRF activity. The EL-TRF activity of cloned IL-2 can also be inhibited by antibody to the IL-2 receptor. The other material with EL-TRF activity has a molecular weight of approximately 32,000. This material lacks IL-2 activity. Antibody to the IL-2 receptor does not impair its function. B cells stimulated with anti-IgM and BSF-p1, with or without B15-TRF, express determinants that react with two monoclonal antibodies which recognize distinct epitopes on the T cell IL-2 receptor. These determinants are present at much lower density (approximately 100-fold) on stimulated B cells that on HT-2 cells, an IL-2-dependent T cell line. Very small amounts of [3H]IL-2 (less than 1,000 molecules per cell) bind to activated B cells. These results indicate that IL-2 binds to a receptor on appropriately prepared B cells and causes them to differentiate into high rate IgM-synthesizing cells. The physiologic significance of the B cell differentiative activity of IL-2 remains to be investigated.

Animals↗
PubMed1984

Ig RNA expression in normal B cells stimulated with anti-IgM antibody and T cell-derived growth and differentiation factors.

An increase in mRNA encoding the secretory form of the mu heavy (H) chain (mus) and in the ratio of mus mRNA to the mRNA encoding the membrane form of the microH chain (micron) occurs in normal B cells stimulated with anti-IgM and BSF-p1 together with the two B cell differentiation factors B15-TRF and EL-TRF. Stimulation of cells with anti-IgM and BSF-p1 with either B15- or EL-TRF causes no change in mus levels or mus/micron ratios. The requirements for induction of high rate IgM synthesis in normal B cells stimulated with anti-IgM were precisely the same as those required for elevation of mus, mRNA levels and for increase in mus/micron mRNA ratios. A very close correlation also exists between induction of mRNA for J chain and increase in mus mRNA levels. Similarly, the increase in J chain protein concentration and percent of cells with cytoplasmic IgM were correlated to each other and to levels of mus and J chain mRNA. These results indicate that elevation of mus mRNA and mus/micron mRNA ratios occur in normal B cells only upon commitment to IgM synthesis, and reaffirm the close relation between IgM synthesis and the presence of J chain.

Animals↗
PubMed1984

Fine structural studies of cholecystokinin-8-like immunoreactive neurons and axon terminals in the nucleus of tractus solitarius of the rat.

Cholecystokinin (CCK)-8-like immunoreactive structures in the nucleus of tractus solitarius (NTS) were studied by using the peroxidase-antiperoxidase (PAP) immunohistochemical method. Immunoreactivity was localized in cell bodies and nerve fibers. The perikarya were oval or fusiform (average length 13 micron) and were mostly located in the dorsal half of the medial subnucleus of the NTS at the level of the area postrema (AP). One to three straight immunoreactive dendritelike processes emerged from the perikarya. Neurons that had first been identified under light microscopy were also studied by electron microscopy. Each neuron had a moderate amount of cytoplasm and an oval or elongated nucleus that was eccentrically located in the soma. A few synaptic inputs were found on the CCK immunoreactive perikarya, while a moderate number were seen on both proximal and distal dendrites. These neurons received both asymmetrical and symmetrical synaptic inputs. The immunoreactive dendrites were most frequently in asymmetrical synaptic contact with nonreactive boutons (max. 2.7 micron in diameter) containing fairly densely packed, small round vesicles. CCK immunoreactive boutons located in the NTS at the level of the AP were analyzed using electron microscopy; these boutons formed asymmetrical synaptic contact with other neuronal elements. Their postsynaptic targets were immunoreactive and nonreactive perikarya and dendrites. These data suggest that CCK-containing afferents might affect the neurotransmission of heterogenous types of solitary neurons.

Animals↗
PubMed1984

Cholecystokinin-8-like immunoreactivity in the pre- and post-central gyri of the human cerebral cortex.

Cellular localization of cholecystokinin-8-like immunoreactive (CCK-IR) structures in the pre- and post-central gyri of the human cerebral cortex was examined by indirect immunofluorescence. CCK-IR was localized mostly in perikarya of non-pyramidal cells such as multipolar, bitufted and bipolar cells, and to a lesser extent in medium and small pyramidal cells. CCK-IR fibers were also observed in these gyri, predominantly in layers I and III.

Cerebral Cortex↗
PubMed1984

The augmentation of tumor-specific immunity by virus help. I. Demonstration of vaccinia virus-reactive helper T cell activity involved in enhanced induction of cytotoxic T lymphocyte and antibody responses.

C3H/He mice were immunized to vaccinia virus by inoculating i.p. viable virus. Their spleen cells (SC) were tested for vaccinia virus-reactive helper T cell activity capable of augmenting (a) anti-trinitrophenyl (TNP) cytotoxic T lymphocyte (CTL) response generated from unprimed C3H/He SC (responding cells) or (b) anti-TNP antibody response generated from TNP-primed C3H/He SC (responding cells) by the stimulation with syngeneic SC infected with vaccinia virus and subsequently modified with TNP (virus-self-TNP). The results demonstrate that cultures of responding cells plus 850 rds X-irradiated vaccinia virus-primed SC failed to enhance anti-TNP CTL or plaque-forming cell (PFC) responses when in vitro stimulation was provided by either virus-self or TNP-self alone. In contrast, these cultures resulted in appreciable augmentation of CTL and PFC responses when stimulated by virus-self-TNP. Such a helper activity provided by vaccinia virus-primed SC was revealed to be T cell mediated and antigen specific. These results are discussed in the context of (a) nature of virus helper antigens, (b) mechanism of help and (c) potential of virus help in augmenting CTL and antibody responses to tumor antigens.

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PubMed1984

The augmentation of tumor-specific immunity by virus help. II. Enhanced induction of cytotoxic T lymphocyte and antibody responses to tumor antigens by vaccinia virus-reactive helper T cells.

The present study investigates the role of vaccinia virus-reactive helper T cells in causing enhanced induction of syngeneic tumor immunity. Vaccinia virus-reactive helper T cell activity capable of inducing the augmented generation of cytotoxic T lymphocyte (CTL) or antibody responses was generated in C3H/HeN mice by inoculating i.p. live virus. Immunization of these mice with vaccinia virus-infected syngeneic X5563 plasmacytoma or MH134 hapatoma cells led to augmented induction of immune resistance against the challenge with corresponding viable tumor cells when compared with the incidence of resistance observed in control mice not primed to vaccinia virus. In vitro cytotoxicity tests utilizing spleen cells and serum from mice which resulted in the augmented tumor resistance by virus help have revealed that spleen cells from C3H/HeN mice immune to the X5563 plasmacytoma exhibited appreciable anti-X5563 CTL activity, whereas serum from these mice failed to display any antibody response. In contrast, MH134-immune mice exhibited potent anti-MH134 antibody, but not CTL responses. Such an anti-tumor CTL or antibody response augmented by vaccinia virus-reactive helper T cells was found to be tumor specific. These results are discussed in the context of (a) the functional diversity of tumor antigens, and (b) mechanisms of virus help that are involved in various forms of augmented induction of syngeneic tumor immunity.

Animals↗
PubMed1984

Ontogeny of neuropeptides in the nucleus ventromedialis hypothalami of the rat: an immunohistochemical analysis.

The ontogeny of leucine-enkephalin (ENK)-, cholecystokinin-8 (CCK)-, substance P (SP)- and neurotensin (NT)-like immunoreactive structures were examined in the nucleus ventromedialis hypothalami (vm) of the rat by means of an indirect immunofluorescence method. ENK- (ENKI), SP- (SPI) and CCK-like immunoreactive (CCKI) structures in the vm exhibited very similar ontogenetic developments, though no CCKI cells were detected. ENKI fibers as well as SPI fibers and neurons first appeared at gestational day 21, ENKI neurons at postnatal day 2, and CCKI fibers at postnatal day 1. These structures subsequently increased in number. The maximum content was reached at postnatal day 21 and was observed even in the adult rats (postnatal day 30). On the other hand, NTI fibers first appeared at postnatal day 1; they decreased in number and no or only a few NTI fibers were seen in the adult rats. No NTI cells were seen in the vm.

Animals↗
PubMed1984

Distribution of six neuropeptides in the nucleus tractus solitarii of the rat: an immunohistochemical analysis.

Distribution of substance P-, [Leu]enkephalin-, cholecystokinin-8-, neurotensin-, avian pancreatic polypeptide- and gamma-melanocyte stimulating hormone-like immunoreactive structures were investigated in the nucleus tractus solitarii of the rat by means of the indirect immunofluorescence method. The density of the immunoreactive structures varied markedly according to neuropeptides or subnuclei, with the medial and commissural nuclei containing the highest density. This suggests that the peptides examined play a role in cardiovascular function. However, as seen in the substance P- and [Leu]enkephalin-like immunoreactive structures, these peptides were widely distributed in the nucleus tractus solitarii in addition to the commissural and medial nuclei; a high density of immunoreactive fibers in the ventral, dorsolateral and intermediate subnuclei. In addition to the immunoreactive fiber plexus, a group of immunoreactive cells was also identified in the subnuclei mentioned above. These findings strongly suggest that substance P- and [Leu]enkephalin-like immunoreactive structures are involved not only in cardiovascular function but also in other functions such as respiration, at least in the rat. Finally, the present study demonstrated that the area postrema, particularly its lateral portion, contains various neuropeptide-like structures, both neurons and fibers, substance P-, [Leu]enkephalin-, cholecystokinin-8- and neurotensin-like immunoreactive neurons and fibers, and avian pancreatic polypeptide- and gamma-melanocyte stimulating hormone-like immunoreactive fibers.

Animals↗
PubMed1984

Effects of hapten epitope structure and hapten-self conjugation pattern on T cell specificity and Ir gene control in hapten-self cytotoxic and helper T cell responses.

Mouse strains of H-2b haplotype exhibit much weaker cytotoxic T lymphocyte (CTL) responses to haptens reactive with amino groups of cell surface (NH2-reactive haptens) compared with H-2k strains. However, H-2b strains can generate high CTL responses to haptens reactive with sulfhydryl groups of cell surface (SH-reactive haptens). The present study investigates the role of haptenic structure and hapten-cell surface reaction patterns in influencing the generation of the T cell specificity as well as the H-2-linked genetic control. CTL and helper T cell responses were generated against two structurally related haptens, N-iodoacetyl-N'-(5-sulfonic-1-naphthyl) ethylene-diamine (SH-reactive AEDANS; AED-SH) and 5-sulfo-1-naphthoxy acetic acid N-hydroxysuccinimide ester (NH2-reactive form of AEDANS; AED-NH2) by immunizing C57BL/6N (H-2b) mice with these hapten-modified syngeneic spleen cells. Spleen cells from primed C57BL/6N mice generated strong CTL and helper T cell activities upon in vitro restimulation with the respective hapten-modified self. The generation of potent anti-AED-NH2 CTL and helper T cell responses in C57BL/6N mice sharply contrasted with the failure of NH2-reactive haptens studied thus far to generate strong anti-hapten cytotoxic responses in H-2b mice. Antibodies induced against the above two haptens exhibited extensive cross-reactivity detected by hemagglutination, whereas CTL and helper T cells clearly discriminated the structural difference between AED-NH2 and AED-SH haptens. The hapten specificity in T cell recognition was also observed between AED-NH2 and trinitrophenyl (TNP) haptens, which were demonstrated to functionally modify similar cell surface sites. These results indicate that hapten epitope structure and hapten-cell membrane conjugation patterns influence the generation of H-2-linked genetic control and T cell specificity in anti-hapten self cytotoxic as well as helper T cell responses.

Animals↗
PubMed1984

Enhanced TNP-reactive helper T cell activity and its utilization in the induction of amplified tumor immunity that results in tumor regression.

The present study was designed to investigate the generation of trinitrophenyl (TNP)-reactive helper T cell activity potent enough to induce the regression of a syngeneic tumor; this occurs by augmenting antitumor-specific immunity through T-T cell interaction. Mice whose skin was painted with trinitrochlorobenzene (TNCB) exhibited a variety of anti-TNP T cell responses, including delayed-type hypersensitivity (DTH) and cytotoxic T cell responses, as well as helper T cell activity. Pretreatment of C3H/He mice with TNP-conjugated copolymer of D-glutamic acid and lysine (TNP-D-GL) or cyclophosphamide, which have been shown, respectively, to inactivate TNP-specific suppressor T cells or suppressor T cells in general, exhibited a slight or marginal augmentation of DTH and cytotoxic potentials when tested 5 wk after TNCB painting. In contrast, the same pretreatment regimens induced an appreciably amplified generation of anti-TNP helper T cell activity. This amplified TNP-helper T cell activity was demonstrated to enhance cytotoxic responses to antigens other than TNP in an antigen-nonspecific way. In fact, such helper T cells enhanced antitumor CTL responses when co-cultured with spleen cells from syngeneic X5563 plasmacytoma-bearing mice in the presence of TNBS-modified X5563 tumor cells. This amplified TNP-helper cell system was utilized for its immunotherapeutic potential. When TNCB was injected into X5563 tumor mass of syngeneic C3H/He mice in which the amplified TNP-helper T cell activity had been generated, an appreciable number of growing tumors was observed to regress. This contrasted with the low incidence of tumor regression observed in mice in which TNP-helper activity had been induced by TNCB painting without inactivation of suppressors. Thus, the present model provides an effective immunotherapeutic manipulation for eliciting enhanced in vivo tumor regression, and emphasizes a role of helper T cells in augmentation of syngeneic tumor immunity.

Animals↗
PubMed1984

The role of tumor-specific Lyt-1+2- T cells in eradicating tumor cells in vivo. I. Lyt-1+2- T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity.

The present study determines the Ly phenotype of T cells mediating tumor cell rejection in vivo and investigates some of cellular mechanisms involved in the in vivo protective immunity. C3H/HeN mice were immunized to syngeneic X5563 plasmacytoma by intradermal (i.d.) inoculation of viable X5563 tumor cells, followed by the surgical resection of the tumor. Spleen cells from these immune mice were fractionated by treatment with anti-Lyt antibodies plus complement, and each Lyt subpopulation was tested for the reconstituting potential of in vivo protective immunity in syngeneic T cell-depleted mice (B cell mice). When C3H/HeN B cell mice were adoptively transferred with Lyt-1-2+ T cells from the above tumor-immunized mice, these B cell mice exhibited an appreciable cytotoxic T lymphocyte (CTL) response to the X5563 tumor, whereas they failed to resist the i.d. challenge of X5563 tumor cells. In contrast, the adoptive transfer of Lyt-1+2- anti-X5563 immune T cells into B cell mice produced complete protection against the subsequent tumor cell challenge. Although no CTL or antibody response against X5563 tumors was detected in the above tumor-resistant B cell mice, these mice were able to retain Lyt-1+2- T cell-mediated delayed-type hypersensitivity (DTH) responses to the X5563 tumor. These results indicate that Lyt-1+2- T cells depleted of the Lyt-2+ T cell subpopulation containing CTL or CTL precursors are effective in in vivo protective immunity, and that these Lyt-1+2- T cells implement their in vivo anti-tumor activity without inducing CTL or antibody responses. The mechanism(s) by which Lyt-1+2- T cells function in vivo for the implementation of tumor-specific immunity is discussed in the context of DTH responses to the tumor-associated antigens and its related Lyt-1+2- T cell-mediated lymphokine production.

Animals↗
PubMed1984

Establishment of a tumor-specific immunotherapy model utilizing TNP-reactive helper T cell activity and its application to the autochthonous tumor system.

Preinduction of potent hapten-reactive helper T cell activity and subsequent immunization with hapten-coupled syngeneic tumor cells result in enhanced induction of tumor-specific immunity through T-T cell collaboration between anti-hapten helper T cells and tumor-specific effector T cells. On the basis of this augmenting mechanism, a tumor-specific immunotherapy protocol was established in which a growing tumor regresses by utilizing a potent trinitrophenyl (TNP)-helper T cell activity. C3H/He mice were allowed to generate the amplified (more potent) TNP-helper T cell activity by skin painting with trinitrochlorobenzene (TNCB) after pretreatment with cyclophosphamide. Five weeks later, the mice were inoculated intradermally with syngeneic transplantable X5563 tumor cells. When TNCB was injected into X5563 tumor mass, an appreciable number of growing tumors, in the only group of C3H/He mice in which the amplified TNP-helper T cell activity had been generated were observed to regress (regressor mice). These regressor mice were shown to have acquired tumor-specific T cell-mediated immunity. Such immunity was more potent than that acquired in mice whose tumor was simply removed by surgical resection. These results indicate that in situ TNP haptenation of the tumor cells in TNP-primed mice can induce the enhanced tumor-specific immunity leading to the regression of a growing tumor. Most importantly, the present study further investigates the applicability of this TNP immunotherapy protocol to an autochthonous tumor system. The results demonstrate that an appreciable percent of growing methylcholanthrene-induced autochthonous tumors regressed by the above TNP immunotherapy protocol. Thus, the present model provides an effective maneuver for tumor-specific immunotherapy in syngeneic transplantable as well as autochthonous tumor systems.

Animals↗
PubMed1984

Establishment of three PPD-reactive helper T cell clones with distinct functions in B cell activation.

Three PPD-reactive long-term cultured helper T cell clones were established from Mycobacterium tuberculosis (Tbc)-primed spleen cells. Clones B11.15 and B12.F were derived from C57BL/6 mice, and clone D-2 was originated from DBA/2Ha mice that have an X-linked recessive inheritance of T cell-replacing factor (TRF) unresponsiveness. Proliferative responses of these cloned T cells were induced by stimulation with PPD in a dose-dependent manner only when I-A-subregion compatible antigen-presenting cells (APC) were present. These three T cell clones have distinct helper functions in B cell activation. Clone B11.15 activated DNP-primed B cells to induce anti-DNP IgM plaque-forming cell (PFC) responses only when high amounts of PPD (5 micrograms) were added to the culture in a major histocompatibility complex (MHC)-unrestricted manner (factor-mediated interaction), whereas stimulation with a low amount of DNP-PPD (0.05 microgram) was ineffective. On the other hand, clone D-2 triggered B cells in the presence of a low amount of DNP-PPD in a MHC-restricted manner (cognate interaction). Significant helper activity of D-2, however, was not observed in the presence of high amounts of PPD. Clone B12.F was able to activate B cells in the presence of either DNP-PPD or PPD. Moreover, both B11.15 and B12.F produced helper factor(s) such as TRF by stimulation with high amounts of PPD in the presence of syngeneic APC, whereas D-2 did not produce measurable helper factor(s) under the same conditions. These results suggest that at least three distinctly functioning PPD-reactive helper T cells can be generated by active immunization with Tbc in vivo. T-B cell interaction between distinctly functioning T cell clones and B cells from (DBA/Ha X C57BL/6) (DB6)F1 male or female mice was then examined. B cells from DB6F1 female mice were triggered by both B11.15 and B12.F in a factor-mediated manner and were also activated with B12.F or D-2 in cognate manner. On the other hand, B cells from DB6F1 male mice, which are TRF low responders, were activated by B12.F or D-2 only through cognate interaction, and they failed to cooperate with B12.F or B11.15 in factor-mediated manner. These findings further suggest that B cells can be triggered by at least two distinct helper T cell subpopulations via respective pathways (cognate interaction and factor-mediated interaction).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Tolerance induction in tumor-specific effector T cells by presensitization with tumor antigens via the intragastric route.

The present study deals with the influence of presensitization with tumor antigens via the intragastric route on the development of syngeneic tumor-specific immunity. Tumor-specific T cell-mediated immunity could be induced in C3H/He mice by intradermal inoculation of syngeneic X5563 tumor cells, followed by the surgical resection of the tumor 7 days later (immunization procedure). However, when the mice were presensitized intragastrically (ig) with 10(8) X-irradiated (10,000 R) tumor cells for four consecutive days, these mice failed to show in vivo protective immunity even after the above immunization procedure. Winn assays performed with spleen cells from mice presensitized ig with X5563 tumor cells revealed that ig-induced suppression was specific for the tumor antigen used for the presensitization, and that suppressor cell activity was not detected in the induction or implementation of in vivo tumor-specific effector cell activity. It was also demonstrated that such unresponsiveness was accompanied by failure to develop delayed-type hypersensitivity and cytotoxic T cell responses to X5563 tumor antigens. These results are discussed in the light of the effect of presensitization with tumor antigens via inappropriate routes on the subsequent induction of in vivo tumor-specific immunity and in relation to the tumor escape mechanism which could occur in gastrointestinal cancers.

Animals↗
PubMed1984

[Tumor-specific immunotherapy: active immunotherapy by augmenting the induction of tumor-specific effector T cells through a T-T cell interaction mechanism].

Recent progress in tumor-specific immunotherapy was reviewed. Methods involved include a) utilization of tumor-specific monoclonal antibodies in conjugation with various anti-cancer agents, b) adoptive transfer of anti-tumor effector T cell clones elaborated in vitro in the presence of interleukin-2 and c) active tumor-specific immunotherapy by augmenting the generation of tumor specific effector T cells. This paper focused especially on the amplified induction of tumor-specific immunity by T-T cell interaction between helper T cells and anti-tumor effector T cells. Data were provided indicating successful tumor-specific immunotherapy in autochthonous as well as syngeneic tumor models and such results were discussed in the light of the future clinical application of the tumor-specific active immunotherapy.

Animals↗