2001年3月
Critical contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4(+) T cells in HIV-1-infected hu-PBL-NOD-SCID mice
JOURNAL OF EXPERIMENTAL MEDICINE
- 巻
- 193
- 号
- 5
- 開始ページ
- 651
- 終了ページ
- 659
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1084/jem.193.5.651
- 出版者・発行元
- ROCKEFELLER UNIV PRESS
Apoptosis is a key for CD4(+) T cell destruction in HIV-1-infected patients. In this study, human peripheral blood lymphocyte (PBL)-transplanted nonobese diabetic (NOD)-severe combined immunodeficient (SCID) (hu-PBL-NOD-SCID) mice were used to examine in vivo apoptosis after HIV-1 infection. As the hu-PBL-NOD-SCID mouse model allowed us to see extensive infection with HIV-1 and to analyze apoptosis in human cells in combination with immunohistological methods, we were able to quantify the number of apoptotic cells with HIV-1 infection. As demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), massive apoptosis was predominantly observed in virus-uninfected CD4(+) T cells in the spleens of HIV-1-infected mice. A combination of TUNEL and immunostaining for death-inducing tumor necrosis factor (TNF) family molecules indicated that the apoptotic cells were frequently found in conjugation with TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD3(+)CD4(+) human T cells. Administration of a neutralizing anti-TRAIL mAb in HIV-1-infected mice markedly inhibited the development of CD4(+) T cell apoptosis. These results suggest that a large number of HIV-1-uninfected CD4(+) T cells undergo TRAIL-mediated apoptosis in HIV-infected lymphoid organs.
- リンク情報
- ID情報
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- DOI : 10.1084/jem.193.5.651
- ISSN : 0022-1007
- Web of Science ID : WOS:000167522500012