Search PubMed⌕ Search

Biomedical subjects

K Inaba

Publications and source records attributed to K Inaba.

At least 235 records · Page 13Linked to original sources
PubMed1985

Properties of memory T lymphocytes isolated from the mixed leukocyte reaction.

During the primary mixed leukocyte reaction, T lymphocytes of the lyt-2- helper subclass proliferate in response to transplantation antigens on allogeneic dendritic cells. We have isolated populations of antigen-specific proliferating lymphoblasts and recultured them in fresh medium. Within 2 days, the blasts become smaller in size, lose responsiveness to T-cell growth factor or interleukin 2, but retain vigorous reactivity to the original alloantigen. Two new biologic properties of these "memory" lymphocytes have been noted. First, they primarily respond to alloantigen on dendritic cells, whereas freshly sensitized lymphoblasts react to allogeneic dendritic cells, macrophages, and B lymphocytes. Second, the memory lymphocytes quickly aggregate with dendritic cells that are either syngeneic or allogeneic, but not with B cells. The aggregates that form with syngeneic dendritic cells disassemble within hours and do not release interleukin 2 or proliferate. The aggregates that form with allogeneic dendritic cells remain intact, release large amounts of interleukin 2 on the first day of culture, and synthesize DNA on the second day. Therefore, dendritic cells actively cluster memory lymphocytes by an antigen-independent mechanism, and this may underlie the heightened functional activity of each cell type.

Antigen-Presenting Cells↗
PubMed1985

Direct and indirect effects of interferon on in vivo murine tumor cell growth.

We cloned two sublines (S1 and R1) of murine Meth A fibrosarcoma cells with respect to their sensitivity to a murine alpha/beta-interferon (IFN) preparation. The growth of S1 cells was suppressed and that of R1 cells was hardly affected by IFN in vitro. This was also the case with cells enclosed in cell-impermeable diffusion chambers in peritoneal cavities. Nevertheless, IFN suppressed the growth of not only S1 cells but also R1 cells in mice inoculated i.p. with these cells, and the survival rates of both S1 cell recipients and R1 cell recipients were markedly improved. S1 cells were observed microscopically to be injured by the direct effect of IFN in vitro and in vivo, but R1 cells in in vitro culture with IFN and those surviving in vivo in the presence of IFN appeared to proliferate well. In the peritoneal cavity of R1 recipients treated daily with IFN, the recruitment of macrophages was enhanced in comparison with untreated R1 recipients. Adherent peritoneal exudate cells obtained from IFN-treated, R1-bearing mice were highly suppressive for the in vitro growth of not only R1 cells but also allogeneic and human cells. The role of macrophages in the indirect effect of IFN on tumor cell growth is discussed.

Animals↗
PubMed1985

Stimulation of the primary mixed leukocyte reaction.

This article will review the evidence that dendritic cells are specialized stimulator cells for the mixed leukocyte reaction. The topics to be considered are (1) identification of dendritic cells, (2) specialized stimulating capacity of dendritic cells in the allogeneic and syngeneic mixed leukocyte reactions, (3) stimulator cells for the secondary mixed leukocyte reaction, and (4) evidence for a role of dendritic cells during graft rejection in situ.

Animals↗
PubMed1984

Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release.

Previous studies have shown that unprimed or resting T lymphocytes will grow and release lymphokines when stimulated by dendritic cells (DC). We now have examined the stimulatory requirements for antigen-primed or blast-transformed T cells. The latter were derived from dendritic/T cell clusters that developed during the primary mixed leukocyte reaction (MLR). The specificity of the blasts was established by a binding assay in which most T cells aggregated small B lymphocytes of the appropriate haplotype within 2 h at 4 or 37 degrees C. Since unprimed T cells did not aggregate allogeneic B cells, we suggest that DC induce T lymphocytes to express additional functioning receptors for antigen. Lyt-2-T blasts did not grow or release interleukin 2 or B cell helper factors unless rechallenged with specific alloantigen, whereupon growth (generation time of 14-18 h) and lymphokine release rapidly resumed. The blasts could be stimulated by allogeneic macrophages, B cells, and B lymphoblasts, whereas the primary MLR was initiated primarily by DC. responsiveness appeared restricted to the I region of the major histocompatibility complex, and varied directly with the level of Ia antigens on the stimulator cells. The interaction of B cells and T blasts was bidirectional. The T blasts would grow and form B cell helper factors, while the B cells grew and secreted antibody. However, the efficacy of T cell-mediated antibody formation was enhanced some 10-fold by the addition of specific antigen. Therefore, responses of resting helper T cells, then, are initiated by antigen plus DC. Once sensitized, T blasts interact independently with antigen presented by other leukocytes.

Animals↗
PubMed1984

Stimulation of lymphokine release from T lymphoblasts. Requirement for mRNA synthesis and inhibition by cyclosporin A.

Three-day, concanavalin A-induced T lymphoblasts have been used as a model to study lymphokine release from sensitized T cells. The blasts responded to interleukin 2 (IL-2) but did not constitutively produce this or other lymphokines. After mitogen restimulation, blast cells synthesized IL-2 as well as gamma-interferon, B cell-stimulating factor(s), and cytolytic differentiation factor(s). This production resulted from the induction of biologically active lymphokine mRNA. Cyclosporin A (CSA), a potent immunosuppressive agent, strongly inhibited synthesis of IL-2, gamma-interferon, and B cell- and CTL-stimulating factor(s), from mitogen-restimulated T blasts. In contrast, CSA did not block the cytolytic activity of the T blasts, nor modify bulk protein synthesis induced by Con A. CSA also blocked lymphokine release from a phorbol myristate acetate-stimulated thymoma cell line, EL-4. The effect of CSA was to block the induction of active lymphokine mRNA, as assayed in an oocyte translation system. This selective inhibition of lymphokine mRNA suggests that CSA may be useful in the therapy of inflammatory, lymphokine-mediated disease states.

Animals↗
PubMed1984

Clustering of dendritic cells, helper T lymphocytes, and histocompatible B cells during primary antibody responses in vitro.

Mouse spleen suspensions generate discrete cell clusters within 1-2 d of culture. We have isolated these clusters by velocity sedimentation to study their contribution to primary antibody responses. Clusters represent approximately 5% of the starting spleen cells and consist of 20-50% B cells, 20-50% T cells, and 10-20% dendritic cells (DC). When the cultures are stimulated with thymus-dependent antigens, like heterologous red cells or dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), the clusters are the principal site for the development of plaque-forming cells (PFC). Noncluster fractions form few PFC and only when supplemented with fresh DC. PFC responses in all cases are antigen specific. B cells cluster only in the presence of T cells and DC (1 DC/200 B-T cell mixtures) and only after encountering specific antigen. The elimination of either DC or Lyt-1+2- T cells, with monoclonal antibody and complement, ablates B cell development into PFC. PFC responses are restored with antigen-nonspecific helper factors formed in the syngeneic mixed leukocyte reaction between DC and T cells. Since PFC to DNP-KLH do not develop de novo when B cells are exposed to antigen and helper factors, anti-DNP PFC precursors must be stimulated within clusters to become responsive to helper factors. PFC development within clusters is restricted by the major histocompatibility complex (MHC). When DC and T cells are from strain P1, then P1 but not P2 B cells develop into PFC; when DC are from strain P2 and T cells from strain P1, strain P2 B cells are selected to become PFC in clusters. The entry of B cells into clusters is itself MHC restricted, since P1 DC/T cells aggregate six times as many B cells from strain P1 as strain P2. Thus, clusters are the site in which DC, B, and T cells interact to generate PFC. One can use clusters to retrieve B cells that have been selected in an antigen-dependent, MHC-restricted fashion and to show that clustering B cells become responsive to soluble, polyclonal helper factors.

Animals↗
PubMed1984

Inclusion complexation of prostaglandin F2 alpha with gamma-cyclodextrin in solution and solid phases.

A solid complex of prostaglandin F2 alpha (dinoprost) with gamma-cyclodextrin in a molar ratio of 1:1 was obtained on the basis of the BS-type phase solubility diagram. The mode of interaction in the solid state was studied by powder X-ray diffractometry, thermal analysis, and carbon-13 cross polarization/magic angle spinning nuclear magnetic resonance (13C-CP/MAS-NMR) spectrometry. The X-ray diffraction and NMR data suggested that prostaglandin F2 alpha is included in the cylindrical channels formed by coaxial alignment of gamma-cyclodextrin molecules to give a channel type structure. Dissolution and thermal behaviors of the prostaglandin F2 alpha-gamma-cyclodextrin complex were examined and compared with the drug itself. The result indicated that the gamma-cyclodextrin complex may have great utility as a rapidly dissolving form of prostaglandin F2 alpha with improved thermal stability.

Cyclodextrins↗
PubMed1984

Autostimulatory adherent cells in the spleen of aging mice: characterization in the syngeneic host-versus-graft reaction.

Enlargement of the popliteal lymph node (PLN) of 6-week-old mice were elicited by the footpad injection of spleen cells of sex-matched, syngeneic, older mice, but not of 6-week-old mice, in a fashion of host-vs.-graft reaction. Effective stimulating cells in the inoculum seem to be Ia-bearing adherent cells. On the other hand, neither B and T cells nor immunoglobulin-secreting cells were effective for host T cell stimulation. Among nonlymphocytic adherent cells, only those attached to plastic dishes after a 24 h-incubation, enriched in macrophages, showed the stimulatory activity for the young recipients, while cells which had adhered once but detached and became non-adherent during a 24 h-incubation or a crude non-macrophage fraction did not induce the PLN response. Thus, the age-related antigenic change may occur on macrophages but not on dendritic cells. The effective cells should be alive, heat-killed cells being impotent to elicite the response. Such spleen adherent cells of aged mice were found to be also stimulative for age-matched recipients, when they are older than 3 months. Autostimulation by macrophages might be responsible, at least in part, for the age-related change of immune functions.

Aging↗
PubMed1984

High-dose 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitro sou rea hydrochloride (ACNU) with autologous bone marrow rescue for patients with brain stem tumors.

4 patients with brain stem tumors were treated with high-dose ACNU with autologous bone marrow rescue. Hematologic and nonhematologic toxicities were not profound. There was objective evidence of response in 2 out of the 4. All were alive for 11-21 months from onset. Safe administration of high-dose ACNU with marrow rescue will warrant further control studies to determine its superiority over conventional doses.

Astrocytoma↗
PubMed1984

Ontogeny of 'macrophage' function. IV. Newborn mouse macrophages strongly suppress tumour cell growth and readily acquire cytolytic activity in comparison with adult macrophages.

Peritoneal macrophages (PM) were prepared as adherent peritoneal exudate cells from newborn and adult mice injected i.p. with thioglycollate medium 4 days previously. In comparison with adult PM, newborn PM exerted a high suppressive effect on the in vitro growth of syngeneic and allogeneic tumour cells, though they did not manifest cytolytic activity. The high suppressive activity of newborn PM was maintained until about 2 weeks of age, and then declined rapidly until about 3 weeks of age toward the level of adult PM. The treatment with a high dose of LPS enhanced the suppressive effect of both newborn and adult PM, while a low dose of LPS was effective only for newborn PM. Necessary minimum dose of LPS to make PM significantly cytolytic was lower for newborn PM than for adult PM. Addition of a low concentration of LK to the culture for activating adult PM with LPS resulted in the augmentation of cytolytic activity and the reduction of necessary minimum dose of LPS. Activation of newborn PM by LPS was not affected by the addition of such a low concentration of LK. On the other hand, newborn PM were rapidly activated by LPS as compared with adult PM. LK accelerated the activation of adult PM by LPS. The activity of newborn PM to bind to tumour cells was higher than that of adult PM. These results seem to indicate that newborn PM are activated to some extent inherently or by some intrinsic agents.

Aging↗
PubMed1983

Dendritic cells induce T lymphocytes to release B cell-stimulating factors by an interleukin 2-dependent mechanism.

Dendritic cells (DC) are essential accessory cells for T-dependent antibody responses in culture (1). We have outlined a three-stage mechanism to explain the capacity of DC to stimulate primary antibody responses to heterologous erythrocytes. First, DC induced T cells to produce and to become responsive to interleukin 2 (IL-2). This stage corresponded to the syngeneic mixed leukocyte reaction (2) and involved the clustering of DC and T cells into discrete aggregates. Isolated clusters, representing 5-10% of the culture, were critical for IL-2 release and the production of IL-2-responsive T blasts. In the second stage, IL-2 directly triggered the responsive T cells to release B cell helper factors. This role for IL-2 was documented with a rabbit anti-IL-2 reagent, purified IL-2, and T cells that had been rendered IL-2 responsive by an initial co-culture with DC. T cell growth was not required for IL-2-mediated helper factor release, since irradiated and untreated responders produced similar levels of factor and did so within 3 h of the addition of IL-2. In the final stage, helper factors stimulated the development of antibody-secreting cells from purified B lymphocytes. The helper factors were not H-2 restricted, but for both sheep and horse erythrocytes, the response to factors was antigen dependent and specific. The IL-2 that was present in the DC/T cell-conditioned medium did not act on B cells, since helper activity was neither neutralized nor absorbed by our anti-IL-2 reagent. We conclude that the ability of the DC to induce IL-2 release and responsiveness underlies its capacity to trigger both T and B lymphocyte reactions.

Animals↗
PubMed1983

Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man.

We report that dendritic cells (DC) are necessary and potent accessory cells for anti-sheep erythrocyte responses in both mouse and man. In mice, a small number of DC (0.3-1% of the culture) restores the response of B/T-lymphocyte mixtures to that observed in unfractionated spleen. An even lower dose (0.03-0.1% DC) is needed if the T cells have been primed to antigen. Responses are both antigen and T cell dependent. Selective depletion of DC from unfractionated spleen with the monoclonal antibody 33D1 and complement ablates the antibody response. In contrast to DC, purified spleen macrophages are weak or inactive stimulators. However, when mixed with DC, macrophages can increase the yield of antibody-secreting cells about 2-fold. In man, small numbers (0.3-1%) of blood DC stimulate antibody formation in vitro. Purified human monocytes do not stimulate but in low doses (1% of the culture) inhibit the antibody response. Likewise, selective removal of human monocytes with antibody and complement enhances or accelerates the development of antibody-secreting cells. We conclude that DC are required for the development of T-dependent antibody responses by mouse and human lymphocytes in vitro.

Animals↗
PubMed1983

Dual effects of glutamate on cyclic AMP levels in slices of rat cerebral cortex with an iron-induced epileptic focus.

An epileptic focus not resulting in generalized convulsions was induced by a microinjection of ferric chloride solution into the left anterior cortex of rats. The formation of the epileptic focus was confirmed by the appearance of bilateral spike and slow wave complexes as well as focal isolated spikes in electrocorticograms (ECoGs). The effect of glutamate on cyclic AMP accumulation was examined in incubated slices prepared from four quadrants of the epileptic cortex. In animals showing isolated spikes 8 to 10 days after the microinjection, the effect of glutamate on cyclic AMP accumulation was stimulatory. It was greatest in the left anterior quadrant which included the injection site, but only slight in the left and right posterior quadrants. In animals showing spike and slow wave complexes 30 to 60 days after the microinjection, the stimulatory effect of glutamate was also most pronounced in the left anterior quadrant. In the right anterior and the left posterior quadrants glutamate had almost no effect, while in the right posterior quadrant, glutamate was inhibitory.

Animals↗
PubMed1982

Regional difference in cyclic AMP response to adenosine of rat cerebral cortex with an iron-induced epileptic focus.

A chronic epileptic focus not resulting in generalized convulsions was induced by a microinjection of FeCl3 solution into the left anterior cortex of rats. Cyclic AMP accumulation in response to adenosine was examined in incubated slices from the cerebral cortex of animals that showed bilateral spike and slow wave complex in an electrocorticogram (ECoG) 30 to 60 days after the microinjection. Cyclic AMP accumulation after incubation with adenosine was most marked in slices from the left anterior quadrant of the cortex including a FeCl3-injected site. A medium response was observed in both the left posterior and the right anterior quadrants, but little or no response in the right posterior quadrant of the cortex.

Adenosine↗