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Title: Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.
Authors: Petrovas, Constantinos
Ferrando-Martinez, Sara
Gerner, Michael Y
Casazza, Joseph P
Pegu, Amarendra
Deleage, Claire
Cooper, Arik
Hataye, Jason
Andrews, Sarah
Ambrozak, David
Del Río Estrada, Perla M
Boritz, Eli
Paris, Robert
Moysi, Eirini
Boswell, Kristin L
Ruiz-Mateos, Ezequiel
Vagios, Ilias
Leal, Manuel
Ablanedo-Terrazas, Yuria
Rivero, Amaranta
Gonzalez-Hernandez, Luz Alicia
McDermott, Adrian B
Moir, Susan
Reyes-Terán, Gustavo
Docobo, Fernando
Pantaleo, Giuseppe
Douek, Daniel C
Betts, Michael R
Estes, Jacob D
Germain, Ronald N
Mascola, John R
Koup, Richard A
metadata.dc.subject.mesh: Adult
Antibodies, Bispecific
CD8-Positive T-Lymphocytes
HIV Antibodies
HIV Infections
Lymph Nodes
Middle Aged
Palatine Tonsil
Issue Date: 2017
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.
metadata.dc.identifier.doi: 10.1126/scitranslmed.aag2285
Appears in Collections:Producción 2020

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