Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies

C Petrovas, S Ferrando-Martinez, MY Gerner… - Science translational …, 2017 - science.org
C Petrovas, S Ferrando-Martinez, MY Gerner, JP Casazza, A Pegu, C Deleage, A Cooper…
Science translational medicine, 2017science.org
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 …
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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