Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15242
Title: Yeast-derived human immunodeficiency virus type 1 p55(gag) virus-like particles activate dendritic cells (DCs) and induce perforin expression in Gag-specific CD8(+) T cells by cross-presentation of DCs
Authors: Tsunetsugu-Yokota, Yasuko
Morikawa, Yuko
Isogai, Maya
Kawana-Tachikawa, Ai
Odawara, Takashi
Nakamura, Tetsuya
Grassi, Maria Fernanda Rios
Autran, Brigitte
Iwamoto, Aikichi
Affilliation: National Institute of Infectious Diseases. Department of Immunology. Shinjuku-ku
Kitasato University. Kitasato Institute for Life Sciences
National Institute of Infectious Diseases. Department of Immunology. Shinjuku-ku
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Tokyo
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Tokyo
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Tokyo
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
Hôpital Pitié-Salpêtrière. Laboratoire d’Immunologie Cellulaire et Tissulaire. Paris, France
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Tokyo
Abstract: To evaluate the immunogenicity of human immunodeficiency virus (HIV) type 1 p55(gag) virus-like particles (VLPs) released by budding from yeast spheroplasts, we have analyzed the effects of yeast VLPs on monocyte-derived dendritic cells (DCs). Yeast VLPs were efficiently incorporated into DCs via both macropinocytosis and endocytosis mediated by mannose-recognizing receptors, but not the mannose receptor. The uptake of yeast VLPs induced DC maturation and enhanced cytokine production, notably, interleukin-12 p70. We showed that yeast membrane components may contribute to DC maturation partly through Toll-like receptor 2 signaling. Thus, Gag particles encapsulated by yeast membrane may have an advantage in stimulating Gag-specific immune responses. We found that yeast VLPs, but not the control yeast membrane fraction, were able to activate both CD4(+) and CD8(+) T cells of HIV-infected individuals. We tested the effect of cross-presentation of VLP by DCs in two subjects recruited into a long-term nonprogressor-slow progressor cohort. When yeast VLP-loaded DCs of these patients were cocultured with peripheral blood mononuclear cells for 7 days, approximately one-third of the Gag-specific CD8(+) T cells were activated and became perforin positive. However, some of the Gag-specific CD8(+) T cells appeared to be lost during in vitro culture, especially in a patient with a high virus load. Our results suggest that DCs loaded with yeast VLPs can activate Gag-specific memory CD8(+) T cells to become effector cells in chronically HIV-infected individuals, but there still remain unresponsive Gag-specific T-cell populations in these patients.
Keywords: HIV-1
Dendritic Cells
Interleukin-12
CD8-Positive T-Lymphocytes
Interferon-gamma
Membrane Glycoproteins
Humans
Protein Precursors
Issue Date: 2003
Publisher: American Society for Microbiology
Citation: TSUNETSUGU-YOKOTA, Y. et al. Yeast-derived human immunodeficiency virus type 1 p55(gag) virus-like particles activate dendritic cells (DCs) and induce perforin expression in Gag-specific CD8(+) T cells by cross-presentation of DCs. Journal of Virology, v. 77, n. 19, p. 10250–10259, 2003.
ISSN: 0022-538X
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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