@article{c32aaeab447247a9bfb6c5a55ac9835c,
title = "Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence",
abstract = "Lymph nodes (LN) and their resident T follicular helper CD4+ T cells (Tfh) are a critical site for HIV replication and persistence. Therefore, optimizing antiviral activity in lymphoid tissues will be needed to reduce or eliminate the HIV reservoir. In this study, we retained effector immune cells in LN of cART-suppressed, SIV-infected rhesus macaques by treatment with the lysophospholipid sphingosine-1 phosphate receptor modulator FTY720 (fingolimod). FTY720 was remarkably effective in reducing circulating CD4+ and CD8+ T cells, including those with cytolytic potential, and in increasing the number of these T cells retained in LN, as determined directly in situ by histocytometry and immunohistochemistry. The FTY720-induced inhibition of T cell egress from LN resulted in a measurable decrease of SIV-DNA content in blood as well as in LN Tfh cells in most treated animals. In conclusion, FTY720 administration has the potential to limit viral persistence, including in the critical Tfh cellular reservoir. These findings provide rationale for strategies designed to retain antiviral T cells in lymphoid tissues to target HIV remission.",
author = "Maria Pino and Sara Paganini and Claire Deleage and Kartika Padhan and Harper, {Justin L.} and King, {Colin T.} and Luca Micci and Barbara Cervasi and Mudd, {Joseph C.} and Gill, {Kiran P.} and Jean, {Sherrie M.} and Kirk Easley and Guido Silvestri and Estes, {Jacob D.} and Constantinos Petrovas and Lederman, {Michael M.} and Mirko Paiardini",
note = "Funding Information: This research is supported by NIH R33AI116171 to Michael Lederman, NIH P01AI131338 to Dr. Mirko Paiardini, and by NIH Office of the Director, Office of Research Infrastructure Programs, P51OD011132. We gratefully acknowledge Gilead (Romas Geleziunas), and ViiV (Jim Demarest and Katie Kitrinos) for supplying the antiretroviral drugs. The authors also thank Stephanie Ehnert and Christopher Souder (Research Resources), and all the animal care and veterinary staff at the YNPRC for providing animal and veterinary care. The SIVmac239 strain used to infect the RMs was kindly provided by Koen Van Rompay (UC Davis). Plasma viral loads were conducted by Thomas Vanderford, and Melon T. Nega at the Emory Center for AIDS Research (CFAR) Virology and Molecular Biomarkers Core. Cell-associated SIV-DNA and SIV-RNA were analyzed by Jeffrey Lifson, AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research. Publisher Copyright: Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.",
year = "2019",
doi = "10.1371/journal.ppat.1008081",
language = "English (US)",
volume = "15",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "10",
}