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PLoS Pathog. 2019 Oct 18;15(10):e1008081. doi: 10.1371/journal.ppat.1008081. eCollection 2019 Oct.

Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence.

Author information

1
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
2
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, United States of America.
3
Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
4
Flow Cytometry Core, Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America.
5
Center for AIDS Research, Department of Medicine, Case Western Reserve University and University Hospitals, Cleveland Medical Center, Cleveland, Ohio, United States of America.
6
Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
7
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
8
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
9
Vaccine and Gene Therapy Institute at Oregon Health Science Center, Portland, Oregon, United States of America.

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.

PMID:
31626660
PMCID:
PMC6834281
DOI:
10.1371/journal.ppat.1008081
[Indexed for MEDLINE]
Free PMC Article

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