%0 Journal Article
%A Petrovas, Constantinos
%A Ferrando-Martinez, Sara
%A Gerner, Michael Y.
%A Casazza, Joseph P.
%A Pegu, Amarendra
%A Deleage, Claire
%A Cooper, Arik
%A Hataye, Jason
%A Andrews, Sarah
%A Ambrozak, David
%A Del Rio Estrada, Perla M.
%A Boritz, Eli
%A Paris, Robert
%A Moysi, Eirini
%A Boswell, Kristin L.
%A Ruiz-Mateos, Ezequiel
%A Vagios, Ilias
%A Leal, Manuel
%A Ablanedo-Terrazas, Yuria
%A Rivero, Amaranta
%A Alicia Gonzalez-Hernandez, Luz
%A McDermott, Adrian B.
%A Moir, Susan
%A Reyes-Teran, Gustavo
%A Docobo, Fernando
%A Pantaleo, Giuseppe
%A Douek, Daniel C.
%A Betts, Michael R.
%A Estes, Jacob D.
%A Germain, Ronald N.
%A Mascola, John R.
%A Koup, Richard A.
%T Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies
%D 2017
%@ 1946-6234
%U http://hdl.handle.net/10668/18997
%X 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.
%K Human-immunodeficiency-virus
%K Lymph-nodes
%K Replication
%K Effector
%K Lymphocytes
%K Activation
%K Responses
%K Tissue
%K Rna
%K Expansion
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