期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 9, 期 373, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aag2285
关键词
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资金
- VRC, NIAID, NIH
- Bill and Melinda Gates Foundation [OPP1032325]
- National Cancer Institute, NIH [HHSN261200800001E]
- Redes Telematicas de Investigacion Cooperativa en Salud (RETICS
- Red de SIDA) [RD12/0017/0029]
- Fondo de Investigacion Sanitaria [PI12/02283, PI13/01912, CP08/00172, CPII14/00025]
- Bill and Melinda Gates Foundation [OPP1032325] Funding Source: Bill and Melinda Gates Foundation
Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals. This profile was associated with persistent local immune activation but did not appear to be directly related to local viral replication. Follicular CD8 (fCD8) T cells, despite compromised cytokine polyfunctionality, showed good cytolytic potential characterized by high ex vivo expression of granzyme B and perforin. We used an anti-HIV/anti-CD3 bispecific antibody in a redirected killing assay and found that fCD8 T cells had better killing activity than did non-fCD8 T cells. Our results indicate that CD8 T cells with potent cytolytic activity are recruited to GCs during HIV infection and, if appropriately redirected to kill HIV-infected cells, could be an effective component of an HIV cure strategy.
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