RRC ID 42072
著者 Tazume K, Hagihara M, Gansuvd B, Higuchi A, Ueda Y, Hirabayashi K, Hojo M, Tanabe A, Okamoto A, Kato S, Hotta T.
タイトル Induction of cytomegalovirus-specific CD4+ cytotoxic T lymphocytes from seropositive or negative healthy subjects or stem cell transplant recipients.
ジャーナル Exp Hematol
Abstract OBJECTIVE:We generated cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) in vitro using dendritic cells (DC) pulsed with crude CMV antigens (Ag).
PATIENTS AND METHODS:Mononuclear cells from healthy CMV-seropositive or seronegative volunteers and from stem cell transplant (SCT) recipients were cultured with CD14(+) monocyte-derived DC prepulsed with CMV Ag and then matured in vitro with lipopolysaccharide and tumor necrosis factor-alpha. After proliferation, cells were checked for phenotype (CD4/CD8), while killing activity was measured by 51Cr-release assay.
RESULTS:CD4(+) T cells, the main proliferating cells from both seropositive and seronegative individuals, killed autologous Ag-pulsed DC but not vehicle-pulsed autologous DC or CMV-pulsed allogeneic DC. Similar CTL induction was accomplished from SCT recipients. Significant killing of autologous CMV-infected fibroblasts required 16-hour incubation as opposed to the standard 4-hour incubation, which was prevented by either a perforin inhibitor or anti-Fas ligand monoclonal antibody. CTL enhanced surface HLA-DR expression of CMV-infected fibroblasts, and their activity was neutralized by anti-HLA-DR monoclonal antibody.
CONCLUSION:CMV-specific CD4(+) CTL were inducible with or without antiviral humoral immunity, even from immunosuppressed SCT recipients. These CTL showed perforin- and Fas/Fas ligand-mediated cytotoxicity after long-term (16-hour) contact with CMV-infected targets.
巻・号 32(1)
ページ 95-103
公開日 2004-1-1
DOI 10.1016/j.exphem.2003.10.008
PII S0301472X03003497
PMID 14725906
MeSH Antigens, Viral / immunology CD4-Positive T-Lymphocytes / immunology* Cytomegalovirus / immunology* Cytomegalovirus Infections / immunology* Cytotoxicity, Immunologic Dendritic Cells / physiology HLA-DR Antigens / analysis Hematopoietic Stem Cell Transplantation* Humans T-Lymphocytes, Cytotoxic / immunology*
IF 2.82
引用数 9
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL HEMATOLOGY
リソース情報
ヒト・動物細胞 MRC-5 K562