Petrovas, ConstantinosFerrando-Martinez, SaraGerner, Michael Y.Casazza, Joseph P.Pegu, AmarendraDeleage, ClaireCooper, ArikHataye, JasonAndrews, SarahAmbrozak, DavidDel Rio Estrada, Perla M.Boritz, EliParis, RobertMoysi, EiriniBoswell, Kristin L.Ruiz-Mateos, EzequielVagios, IliasLeal, ManuelAblanedo-Terrazas, YuriaRivero, AmarantaAlicia Gonzalez-Hernandez, LuzMcDermott, Adrian B.Moir, SusanReyes-Teran, GustavoDocobo, FernandoPantaleo, GiuseppeDouek, Daniel C.Betts, Michael R.Estes, Jacob D.Germain, Ronald N.Mascola, John R.Koup, Richard A.2023-02-122023-02-122017-01-181946-6234http://hdl.handle.net/10668/18997Cytolytic 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.enHuman-immunodeficiency-virusLymph-nodesReplicationEffectorLymphocytesActivationResponsesTissueRnaExpansionresearch articleopen access10.1126/scitranslmed.aag22851946-6242https://europepmc.org/articles/pmc5497679?pdf=render394447000004