Sci Transl Med. 2017 Jan 18; 9(373):NA.

PubMed ID: 28100833

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

Petrovas C, Ferrando-Martinez S, Gerner MY, Casazza JP, Pegu A, Deleage C, Cooper A, Hataye J, Andrews S, Ambrozak D, Del Rio Estrada PM, Boritz E, Paris R, Moysi E, Boswell KL, Ruiz-Mateos E, Vagios I, Leal M, Ablanedo-Terrazas Y, Rivero A, Gonzalez-Hernandez LA, McDermott AB, Moir S, Reyes-Teran G, Docobo F, Pantaleo G, Douek DC, Betts MR, Estes JD, Germain RN, Mascola JR, Koup RA

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.