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


Autoři: Maria Pino aff001;  Sara Paganini aff001;  Claire Deleage aff002;  Kartika Padhan aff003;  Justin L. Harper aff001;  Colin T. King aff001;  Luca Micci aff001;  Barbara Cervasi aff004;  Joseph C. Mudd aff005;  Kiran P. Gill aff004;  Sherrie M. Jean aff006;  Kirk Easley aff007;  Guido Silvestri aff001;  Jacob D. Estes aff009;  Constantinos Petrovas aff003;  Michael M. Lederman aff005;  Mirko Paiardini aff001
Působiště autorů: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America aff001;  AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, United States of America aff002;  Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America aff003;  Flow Cytometry Core, Emory Vaccine Center, Emory University, Atlanta, Georgia, United States of America aff004;  Center for AIDS Research, Department of Medicine, Case Western Reserve University and University Hospitals, Cleveland Medical Center, Cleveland, Ohio, United States of America aff005;  Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America aff006;  Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America aff007;  Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America aff008;  Vaccine and Gene Therapy Institute at Oregon Health Science Center, Portland, Oregon, United States of America aff009
Vyšlo v časopise: Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008081
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008081

Souhrn

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 ART-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.

Klíčová slova:

Blood – Cell staining – Cloning – Cytotoxic T cells – HIV – Lymph nodes – SIV – T cells


Zdroje

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Hygiena a epidemiologie Infekční lékařství Laboratoř

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