Ken-ichi Maeda

Bio: Ken-ichi Maeda is an academic researcher from University of Tokushima. The author has contributed to research in topics: Cytotoxic T cell & Interleukin 21. The author has an hindex of 10, co-authored 22 publications receiving 291 citations. Previous affiliations of Ken-ichi Maeda include Kyushu University.

Gamma delta T cells play an important role in hsp65 expression and in acquiring protective immune responses against infection with Toxoplasma gondii.

Abstract: Previously, we reported that the expression of hsp65 within and on host macrophages correlates closely with protection against infection with Toxoplasma gondii in mice. Herein, we propose that gamma delta T cells play a crucial role in the induction of hsp65 and also in the protective immune response to T. gondii. Intraperitoneal inoculation with this protozoan resulted in hsp65 being expressed on and in host peritoneal macrophages and resulted in an increase of T cells bearing the gamma delta receptor with Thy-1+ and Thy-1- phenotypes in the peritoneal cavity and spleen. When mice were depleted of gamma delta T cells by the administration of a mAb, hsp65 expression was markedly decreased. In contrast, the expression of this protein was rather enhanced and gamma delta T cells were prominently expanded in mice depleted of alpha beta T cells. The protection in mice treated with the mAb paralleled the magnitude of hsp65 expression. Mice depleted of gamma delta T cells died most frequently in the early stages of infection, whereas most of those depleted of alpha beta T cells survived the early stages of lethal infection with T. gondii. However, the latter group of mice did not definitely control the T. gondii infection in its late stages. IFN-gamma was not essential for either the expression of hsp65 or the resistance induced by gamma delta T cells, as demonstrated in mice treated with mAb to murine IFN-gamma. These findings indicated that gamma delta T cells having both the Thy-1+ and Thy-1- phenotypes contribute to hsp65 expression within and on macrophages in an IFN-gamma-independent manner. This, in turn, plays a role in the development of protective immunity during the early stage of this parasitic infection.

Induction of heat shock protein closely correlates with protection against Toxoplasma gondii infection.

Abstract: Heat shock proteins (HSPs) are evolutionarily highly conserved polypeptides that appear to be produced by many cells to preserve cellular functions under a variety of conditions of stress, including infections. We report that a 65-kDa HSP is present in mouse peritoneal cells that have been infected with a low-virulence (Beverley) strain of Toxoplasma gondii, as determined by electroblot assay using a monoclonal antibody specific for microbial HSP65. This HSP is, however, not expressed when infection occurs with the high-virulence RH strain of T. gondii. Furthermore, HSP was demonstrable in mice that acquired resistance against infection with a lethal dose of bradyzoites of the Beverley strain or even of an inoculum of a highly virulent strain of T. gondii (RH). From these results, it can be suggested that HSPs play an important role in developing effective defenses that include effective immune responses against infection with Toxoplasma parasites in vivo.

Selective elimination of double-positive immature thymocytes by a thymic epithelial cell line.

Abstract: A cloned epithelial cell line, TEL-2, has been established from the stroma tissues of normal mouse thymus. Incubation of mouse thymocytes on TEL-2 cells resulted in the selective elimination of double-positive (CD4+CD8+) cells from the culture, whereas single-positive (CD4+CD8- or CD4-CD8+) thymocytes remaining in the culture were concentrated in non-integrated cell population. The CD3- or CD3 low-positive thymocytes were also eliminated by the TEL-2 cells from the culture, followed by the concentration of CD3 high-positive cells in the culture. Only intact viable thymocytes were integrated into TEL-2 cells. Electron microscopic examination showed that the integrated cells into TEL-2 cytoplasm were gradually degenerated. Mature single-positive T cells, mature B cells or double-negative thymocytes were not integrated into TEL-2 cells. The TEL-2 cell may provide information on the mechanism of selective disappearance of double-positive immature cells from the thymus.

CD40 and IFN-gamma dependent T cell activation by human bronchial epithelial cells.

Abstract: We examined whether freshly isolated human bronchial cells (HBEC) and bronchial epithelial cell line/BEAS-2B cells expressed surface molecules required for APC function. These cells expressed CD40 and ICAM-1, but not B7-1, B7-2 or HLA-DR molecules. Treatment of these cells with IFN-gamma resulted in enhanced expression of CD40 and ICAM-1 as well as induction of HLA-DR expression. Th2 cytokines such as IL-4 and IL-5, proinflammatory cytokine of GM-CSF and nonspecific activator endotoxin had no effect on these phenotypic expressions. Functional examinations showed that allogeneic lymphocytes purified from peripheral blood strongly proliferated in response to BEAS-2B cells cultured with IFN-gamma, but only weakly compared with those without IFN-gamma. When allogeneic lymphocytes were purified to CD4+ cells, the proliferative response against BEAS-2B cells was abolished. Blockade of CD40-CD40L interaction by anti-CD40 antibody also inhibited the proliferation of lymphocytes to BEAS-2B cells, although this treatment showed a minimum effect on the response to allogeneic MNC. Thus, bronchial epithelial cells have the ability to present allogeneic antigens to T cells in both CD40- and IFN-gamma-dependent manners under the presence of third party cells that transduce co-stimulatory signals.

Antigen-specific B cells are required for the secondary response of T cells but not for their priming

Abstract: We studied the potential role of B cells in T cell responses using severe-combined immunodeficient (SCID) mice grafted with the thymus from fetal C.B-17 mice (TG mice). These mice developed both CD4+ and CD8+ T cells, but not B cells within 2 months after transplantation. TG mice showed normal delayed-type hypersensitivity responses against the immunizing antigen ovalbumin (OVA). Lymph node (LN) cells of TG mice proliferated well in response to concanavalin A (Con A). Further, Con A stimulation induced the production of interleukin (IL)-2, IL-6 and interferon (IFN)-gamma and the expression of IL-4 mRNA. Thus, TG mice were reconstituted without remarkable immunodeficiency. However, these T cells failed to proliferate to OVA stimulation. Response to OVA was also inhibited in SCID mice grafted with fetal C.B-17 liver cells when B cells were depleted in the proliferation assay. Unresponsiveness against immunizing antigen was restored by the addition of antigen-primed B cells, but not by naive B cells, lipopolysaccharide-activated B cells or B cells primed with sheep red blood cells. Next, we examined whether antigen-primed B cells could induce T cell responses without professional antigen-presenting cells (APC). T and B cells were purified from OVA-immunized mice by cell sorter. These T cells proliferated in response to OVA and produced IFN-gamma in the absence of non-B APC. When anti-CD80 or anti-CD86 was added in the assay, proliferation and IFN-gamma production was inhibited. These results indicate that B cells activated specifically with antigen are required for the secondary response of T cells, but not for their priming.

Apoptosis and Programmed Cell Death in Immunity

Abstract: Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism of apoptosis is currently under active investigation.

Regulation and Function of T-Cell-Mediated Immunity during Toxoplasma gondii Infection

Abstract: The intracellular protozoan Toxoplasma gondii is a widespread opportunistic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining strong T-cell-mediated immunity is crucial in preventing the emergence of T. gondii as a serious pathogen. The parasite induces high levels of gamma interferon (IFN-γ) during initial infection as a result of early T-cell as well as natural killer (NK) cell activation. Induction of interleukin-12 by macrophages is a major mechanism driving early IFN-γ synthesis. The latter cytokine, in addition to promoting the differentiation of Th1 effectors, is important in macrophage activation and acquisition of microbicidal functions, such as nitric oxide release. During chronic infection, parasite-specific T lymphocytes release high levels of IFN-γ, which is required to prevent cyst reactivation. T-cell-mediated cytolytic activity against infected cells, while easily demonstrable, plays a secondary role to inflammatory cytokine production. While part of the clinical manifestations of toxoplasmosis results from direct tissue destruction by the parasite, inflammatory cytokine-mediated immunopathologic changes may also contribute to disease progression.

Lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro.

Abstract: Dendritic cells (DCs; 1) have been purified from mouse spleen in good yield. Spleen cell suspensions were floated on dense bovine plasma albumin (BPA) columns, and the low density fraction was adhered to glass (2). The adherent cells consisted of DCs and immature macrophages most of which eluted in a viable state from the culture dish after overnight incubation. The macrophages were then removed by selective rosetting with opsonized erythrocytes and recentrifugation on dense BPA. This protocol resulted in a purified DC fraction, containing 1--3 X 10(5) DCs/spleen, which was homogeneous and distinctive in its properties. All cells exhibited the phase contrast and transmission electron microscopy (EM) cytologic features that were previously described for freshly isolated adherent DCs. By scanning EM, most purified DCs exhibited a remarkable array of bulbous protrusions of varying length and shape, unlike any other lymphoid cell. All DCs expressed surface Ia and other major histocompatibility complex (MHC)- linked alloantigens. DCs, however, lacked surface Ig and T-cell antigens, and did not bind or interiorize opsonized erythrocytes. Purified DCs have been maintined in vitro for 3 days. Recovery of cultured purified cells was 70% or more of starting cell numbers. When [3H]uridine-tagged DCs were mixed with nonlabeled heterogeneous spleen cells, 70--80% of the labeled DCs were recovered as viable cells 2--3 days later. Purified DCs did not readhere to tissue culture surfaces and did not proliferate, even when cultured with mitogenic doses of concanavalin A and lipopolysaccharide. Finally, DCs did not change their cytologic or surface properties after 3 days of culture. These observations extend the evidence that DCs are a novel cell type and provide useful properties and techniques for their further study.

The CD1 family: a third lineage of antigen-presenting molecules.

Abstract: Publisher Summary This chapter discusses the CD1 structure and function in humans and other mammals, and the manner in which the CD1 family may contribute to the overall maintenance of specific immunity. CD1 has been studied at the serologic, protein, and molecular levels in humans and in several other species including rodents, rabbit, and sheep. Although functional studies of CD1 have so far only been reported using human cells, the stage is now set for the development of animal models for the in vivo exploration of CD1 function. The chapter also presents genetics and molecular biology of the CD1 family, the CD1 proteins: characterization of a family of MHC-related molecules, serologic definition of CD1, biochemical, and immunochemical studies of CD1 proteins, tissue distribution and cellular expression of CD1 proteins, and the immunological function of CD1 proteins. Group 1 CD1 proteins are antigen-presenting molecules in the same sense as the classical MHC class I and II molecules. Although MHC-restricted T cells are predominant in most immune responses, it still remains possible that CD1-restricted responses may take on a substantial importance in certain anatomic sites or in the setting of specific diseases or infections, as CD1 differs from MHC-encoded antigen-presenting molecules in a number of ways. These include their patterns of cellular and tissue expression, the predicted structures of their membrane distal domains, and the chemical nature of the antigens presented. Therefore, an appreciation of how the CD1 system contributes to immunity may well enhance the human ability to manipulate the immune system in predictable and useful ways.