Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence.
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 i...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008081 |
| _version_ | 1818589534282055680 |
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| author | Maria Pino Sara Paganini Claire Deleage Kartika Padhan Justin L Harper Colin T King Luca Micci Barbara Cervasi Joseph C Mudd Kiran P Gill Sherrie M Jean Kirk Easley Guido Silvestri Jacob D Estes Constantinos Petrovas Michael M Lederman Mirko Paiardini |
| author_facet | Maria Pino Sara Paganini Claire Deleage Kartika Padhan Justin L Harper Colin T King Luca Micci Barbara Cervasi Joseph C Mudd Kiran P Gill Sherrie M Jean Kirk Easley Guido Silvestri Jacob D Estes Constantinos Petrovas Michael M Lederman Mirko Paiardini |
| author_sort | Maria Pino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T09:42:10Z |
| format | Article |
| id | doaj.art-317b112ab6a540088ba22b5560bb1102 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T09:42:10Z |
| publishDate | 2019-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-317b112ab6a540088ba22b5560bb11022022-12-21T22:36:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-10-011510e100808110.1371/journal.ppat.1008081Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence.Maria PinoSara PaganiniClaire DeleageKartika PadhanJustin L HarperColin T KingLuca MicciBarbara CervasiJoseph C MuddKiran P GillSherrie M JeanKirk EasleyGuido SilvestriJacob D EstesConstantinos PetrovasMichael M LedermanMirko PaiardiniLymph 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.https://doi.org/10.1371/journal.ppat.1008081 |
| spellingShingle | Maria Pino Sara Paganini Claire Deleage Kartika Padhan Justin L Harper Colin T King Luca Micci Barbara Cervasi Joseph C Mudd Kiran P Gill Sherrie M Jean Kirk Easley Guido Silvestri Jacob D Estes Constantinos Petrovas Michael M Lederman Mirko Paiardini Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. PLoS Pathogens |
| title | Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. |
| title_full | Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. |
| title_fullStr | Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. |
| title_full_unstemmed | Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. |
| title_short | Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence. |
| title_sort | fingolimod retains cytolytic t cells and limits t follicular helper cell infection in lymphoid sites of siv persistence |
| url | https://doi.org/10.1371/journal.ppat.1008081 |
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