Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Science translational medicine, 2017-01, Vol.9 (373)

Ort / Verlag

United States

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.