Abstract:
:HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Chew GM,Fujita T,Webb GM,Burwitz BJ,Wu HL,Reed JS,Hammond KB,Clayton KL,Ishii N,Abdel-Mohsen M,Liegler T,Mitchell BI,Hecht FM,Ostrowski M,Shikuma CM,Hansen SG,Maurer M,Korman AJ,Deeks SG,Sacha JB,Ndhlovu LCdoi
10.1371/journal.ppat.1005349subject
Has Abstractpub_date
2016-01-07 00:00:00pages
e1005349issue
1eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-15-01706journal_volume
12pub_type
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