Research ArticleHIV

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

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Science Translational Medicine  18 Jan 2017:
Vol. 9, Issue 373, eaag2285
DOI: 10.1126/scitranslmed.aag2285

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Follicular CD8 T cells might ferret out HIV

HIV-infected CD4 T cells may lurk in lymphoid follicles that are normally devoid of CD8 T cells, making these areas a safe haven for the viral reservoir. Petrovas et al. examined human lymph nodes and tonsils and somewhat surprisingly found that CD8 T cells did infiltrate follicles in HIV-infected individuals. When compared with cells from healthy individuals, these CD8 T cells were less likely to produce cytokines but were still able to kill target cells, especially when cultured with a bispecific antibody to redirect killing toward HIV-infected cells. The use of bispecific antibodies in patients to provoke follicular CD8 T cells may be a path toward a potential HIV cure.

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.

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