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Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.
- Source :
-
Science translational medicine [Sci Transl Med] 2017 Jan 18; Vol. 9 (373). - Publication Year :
- 2017
-
Abstract
- 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.<br /> (Copyright © 2017, American Association for the Advancement of Science.)
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 9
- Issue :
- 373
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28100833
- Full Text :
- https://doi.org/10.1126/scitranslmed.aag2285