RT Journal Article
T1 Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies
A1 Petrovas, Constantinos
A1 Ferrando-Martinez, Sara
A1 Gerner, Michael Y.
A1 Casazza, Joseph P.
A1 Pegu, Amarendra
A1 Deleage, Claire
A1 Cooper, Arik
A1 Hataye, Jason
A1 Andrews, Sarah
A1 Ambrozak, David
A1 Del Rio Estrada, Perla M.
A1 Boritz, Eli
A1 Paris, Robert
A1 Moysi, Eirini
A1 Boswell, Kristin L.
A1 Ruiz-Mateos, Ezequiel
A1 Vagios, Ilias
A1 Leal, Manuel
A1 Ablanedo-Terrazas, Yuria
A1 Rivero, Amaranta
A1 Alicia Gonzalez-Hernandez, Luz
A1 McDermott, Adrian B.
A1 Moir, Susan
A1 Reyes-Teran, Gustavo
A1 Docobo, Fernando
A1 Pantaleo, Giuseppe
A1 Douek, Daniel C.
A1 Betts, Michael R.
A1 Estes, Jacob D.
A1 Germain, Ronald N.
A1 Mascola, John R.
A1 Koup, Richard A.
K1 Human-immunodeficiency-virus
K1 Lymph-nodes
K1 Replication
K1 Effector
K1 Lymphocytes
K1 Activation
K1 Responses
K1 Tissue
K1 Rna
K1 Expansion
AB 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.
PB Amer assoc advancement science
SN 1946-6234
YR 2017
FD 2017-01-18
LK http://hdl.handle.net/10668/18997
UL http://hdl.handle.net/10668/18997
LA en
DS RISalud
RD Apr 6, 2025