Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.
Details
Serval ID
serval:BIB_6300DD2A65E6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.
Journal
Science translational medicine
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
18/01/2017
Peer-reviewed
Oui
Volume
9
Number
373
Pages
373
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Adult, Aged, Antibodies, Bispecific/immunology, CD8-Positive T-Lymphocytes/cytology, Cytokines/immunology, Female, Granzymes/immunology, HIV Antibodies/immunology, HIV Infections/immunology, Humans, Lymph Nodes/cytology, Male, Middle Aged, Palatine Tonsil/cytology, Perforin/immunology, Phenotype
Pubmed
Web of science
Create date
30/01/2017 19:38
Last modification date
20/08/2019 14:19