@article{1aec7d72575b443dbdede7453527d4f3,
title = "TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection",
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.",
author = "Chew, {Glen M.} and Tsuyoshi Fujita and Webb, {Gabriela M.} and Burwitz, {Benjamin J.} and Wu, {Helen L.} and Reed, {Jason S.} and Hammond, {Katherine B.} and Clayton, {Kiera L.} and Naoto Ishii and Mohamed Abdel-Mohsen and Teri Liegler and Mitchell, {Brooks I.} and Hecht, {Frederick M.} and Mario Ostrowski and Shikuma, {Cecilia M.} and Hansen, {Scott G.} and Mark Maurer and Korman, {Alan J.} and Deeks, {Steven G.} and Sacha, {Jonah B.} and Ndhlovu, {Lishomwa C.}",
note = "Funding Information: The project described was supported in part by several funding agencies: The SCOPE cohort was supported in part by the National Institutes of Allergies and Infectious Diseases (NIAID) (RO1 AI087145, K24 AI069994), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), and the CFAR Network of Integrated Systems (R24 AI067039). This work was supported in part by the National Center for Research Resources (NCCR) grant P51 OD011092 and the NIAID grant P30 AI027763. This Funding was also made possible by collaborative efforts of the Office of AIDS Research, the NIAID, and the International AIDS Society (LCN). Additional support was provided in part with federal funds from the NIAID and NIH contract Number NOI-AI-85341. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",
year = "2016",
doi = "10.1371/journal.ppat.1005349",
language = "English",
volume = "12",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "1",
}