Tetsuya Yoshida

Fukuoka University, Hukuoka, Fukuoka, Japan

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Publications (4)29.16 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A large number of infectious diseases caused by viral or bacterial infections are treatable and/or preventable by vaccination. In addition, ongoing research is aimed at the development of vaccines against other types of diseases, including almost all forms of cancer. The efficacy of a vaccine relies on the antigen-specific response by the entire repertoire of immune competent cells. Here, we have generated a powerful mitogen fusion protein, CD40L-FasL-IgFc, which stimulates CD40(+) cells robustly. We found that this specific cell activation is accompanied by increased expression of PRDI-BF1 (Blim-1) RNA, an indicator of terminal B-cell differentiation, in cultures stimulated with CD40L-FasL-IgFc. The addition of specific inhibitors of NF-kappaB and MEK1/2 partially suppressed the observed proliferative effects of CD40L-FasL-IgFc. When tested in vivo, the immune response to influenza HA vaccine was significantly increased by co-administration of CD40L-FasL-IgFc. Moreover, the co-administration of the cDNA expression plasmid encoding CD40L-FasL-IgFc significantly boosted the vaccine response. We now have a unique opportunity to evaluate our novel fusion protein adjuvant, and other similarly constructed fusion proteins, in both protein-based and genetic vaccines.
    Vaccine 03/2010; 28(21):3688-95. · 3.77 Impact Factor
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    ABSTRACT: CD28 is a cell surface glycoprotein expressed on T cells that modulates immune responses through its ability to transduce costimulatory signals. Even though nearly 50% of the molecular mass of CD28 is N-glycan, the physiological significance of CD28 glycosylation is at present unknown. In this report, we have investigated the function of hypoglycosylated wildtype CD28 and its splice variant, CD28i. When N-glycosylation was prevented through point mutations in N-glycosylation sites in CD28, or reduced by glycosidase inhibitors, the binding of CD28 to CD80 significantly increased. Stimulation of hypoglycosylated CD28 induced IL-2 promoter activity greater than that induced through the stimulation of wildtype CD28. Unlike hypoglycosylated wildtype CD28, hypoglycosylation of CD28i did not alter CD28i functions. Our data indicate that N-glycans of CD28 negatively regulate CD28/CD80 interactions, resulting in diminished CD28 signaling. It is also suggested that N-glycans regulate the density of CD28 clustering upon ligation with CD80/CD86. The results support the hypothesis that the N-glycosylation negatively regulates CD28-mediated T cell adhesion and costimulation.
    Biochemical and Biophysical Research Communications 05/2004; 317(1):60-7. · 2.28 Impact Factor
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    ABSTRACT: The role of CD40 ligand (CD40L)/CD40 signaling in T cell-dependent B cell differentiation and maturation has been amply documented. The mechanism of CD40 signaling in B cells has been well established, whereas the signaling mechanism of CD40L in T cell costimulation remains unknown. In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells. The cross-linking of CD40L resulted in the coendocytosis of CD28i with CD40L. The tyrosine phosphorylation of CD28i followed the cross-linking of CD40L, and the overexpression of CD28i augmented the c-Jun NH2-terminal kinase, p21-activated kinase 2, and nuclear factor kappaB activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells.
    Journal of Experimental Medicine 05/2004; 199(7):1025-31. · 13.21 Impact Factor
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    ABSTRACT: We have characterized a splice variant (isoform) of the human CD28 T cell costimulatory receptor. The nucleotide sequence of this CD28 isoform was identical to that of CD28 in the signal peptide, the transmembrane domain, and the cytoplasmic tail, but it was missing a large segment of the extracellular ligand-binding domain, which is encoded by the second exon. This isoform (CD28i), whose message level exceeded 25% of CD28, was a transmembrane homodimer. CD28i was found noncovalently associated with CD28 and was tyrosine-phosphorylated/PI3-kinase-complexed following the crosslinking of CD28, and the CD28 costimulatory signal was enhanced in T cells expressing CD28i. These data demonstrate that CD28i, via noncovalent association with CD28, plays a role as a costimulatory signal amplifier in human T cells.
    Blood 04/2002; 99(6):2138-45. · 9.78 Impact Factor

Publication Stats

46 Citations
29.16 Total Impact Points

Institutions

  • 2004–2010
    • Fukuoka University
      • Department of Internal Medicine
      Hukuoka, Fukuoka, Japan
    • University Health Network
      Toronto, Ontario, Canada
    • Kyoto University
      • Division of Pharmaceutical Sciences
      Kyoto, Kyoto-fu, Japan
  • 2002
    • The University of Western Ontario
      • Department of Microbiology and Immunology
      London, Ontario, Canada