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.
| Original language | English (US) |
|---|---|
| Article number | eaag2285 |
| Journal | Science Translational Medicine |
| Volume | 9 |
| Issue number | 373 |
| DOIs | |
| State | Published - Jan 18 2017 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. / 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; Germain, Ronald N.; Mascola, John R.; Koup, Richard A.
In: Science Translational Medicine, Vol. 9, No. 373, eaag2285, 18.01.2017.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies
AU - Petrovas, Constantinos
AU - Ferrando-Martinez, Sara
AU - Gerner, Michael Y.
AU - Casazza, Joseph P.
AU - Pegu, Amarendra
AU - Deleage, Claire
AU - Cooper, Arik
AU - Hataye, Jason
AU - Andrews, Sarah
AU - Ambrozak, David
AU - Del Río Estrada, Perla M.
AU - Boritz, Eli
AU - Paris, Robert
AU - Moysi, Eirini
AU - Boswell, Kristin L.
AU - Ruiz-Mateos, Ezequiel
AU - Vagios, Ilias
AU - Leal, Manuel
AU - Ablanedo-Terrazas, Yuria
AU - Rivero, Amaranta
AU - Gonzalez-Hernandez, Luz Alicia
AU - McDermott, Adrian B.
AU - Moir, Susan
AU - Reyes-Terán, Gustavo
AU - Docobo, Fernando
AU - Pantaleo, Giuseppe
AU - Douek, Daniel C.
AU - Betts, Michael R.
AU - Estes, Jacob
AU - Germain, Ronald N.
AU - Mascola, John R.
AU - Koup, Richard A.
PY - 2017/1/18
Y1 - 2017/1/18
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85010304642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85010304642&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aag2285
DO - 10.1126/scitranslmed.aag2285
M3 - Article
C2 - 28100833
AN - SCOPUS:85010304642
VL - 9
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 373
M1 - eaag2285
ER -