Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques
Previous studies have indicated that the loss of CD161-expressing CD4<sup>+</sup> Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/9/1944 |
| _version_ | 1827722938666713088 |
|---|---|
| author | Siva Thirugnanam Edith M. Walker Faith Schiro Pyone P. Aye Jay Rappaport Namita Rout |
| author_facet | Siva Thirugnanam Edith M. Walker Faith Schiro Pyone P. Aye Jay Rappaport Namita Rout |
| author_sort | Siva Thirugnanam |
| collection | DOAJ |
| description | Previous studies have indicated that the loss of CD161-expressing CD4<sup>+</sup> Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8<sup>+</sup> T cells remain unclear. Here, we examined the functions of peripheral blood and mucosal CD161<sup>+</sup>CD8<sup>+</sup> T cells in the macaque model of HIV infection. In contrast to the significant loss of CD161<sup>+</sup>CD4<sup>+</sup> T cells, CD161<sup>+</sup>CD8<sup>+</sup> T cell frequencies were maintained in blood and gut during chronic SIV infection. Furthermore, gut CD161<sup>+</sup>CD8<sup>+</sup> T cells displayed greater IL-17 production and maintained Th1-type and cytolytic functions, contrary to impaired IL-17 and granzyme-B production in CD161<sup>+</sup>CD4<sup>+</sup> T cells of SIV-infected macaques. These results suggest that augmented Th17-type effector functions of CD161<sup>+</sup>CD8<sup>+</sup> T cells during SIV infection is a likely mechanism to compensate for the sustained loss of gut mucosal Th17 cells. Targeting the cytokine and cytolytic effector functions of CD161<sup>+</sup>CD8<sup>+</sup> T cells in the preclinical setting of chronic SIV infection with antiretroviral therapy has implications in the restoration of gut barrier disruption in persons with HIV infection. |
| first_indexed | 2024-03-10T21:51:14Z |
| format | Article |
| id | doaj.art-229954ad75884ee9ba3d2d923ae8c5a3 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T21:51:14Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-229954ad75884ee9ba3d2d923ae8c5a32023-11-19T13:23:55ZengMDPI AGViruses1999-49152023-09-01159194410.3390/v15091944Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus MacaquesSiva Thirugnanam0Edith M. Walker1Faith Schiro2Pyone P. Aye3Jay Rappaport4Namita Rout5Tulane National Primate Research Center, Covington, LA 70433, USATulane National Primate Research Center, Covington, LA 70433, USATulane National Primate Research Center, Covington, LA 70433, USATulane National Primate Research Center, Covington, LA 70433, USATulane National Primate Research Center, Covington, LA 70433, USATulane National Primate Research Center, Covington, LA 70433, USAPrevious studies have indicated that the loss of CD161-expressing CD4<sup>+</sup> Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8<sup>+</sup> T cells remain unclear. Here, we examined the functions of peripheral blood and mucosal CD161<sup>+</sup>CD8<sup>+</sup> T cells in the macaque model of HIV infection. In contrast to the significant loss of CD161<sup>+</sup>CD4<sup>+</sup> T cells, CD161<sup>+</sup>CD8<sup>+</sup> T cell frequencies were maintained in blood and gut during chronic SIV infection. Furthermore, gut CD161<sup>+</sup>CD8<sup>+</sup> T cells displayed greater IL-17 production and maintained Th1-type and cytolytic functions, contrary to impaired IL-17 and granzyme-B production in CD161<sup>+</sup>CD4<sup>+</sup> T cells of SIV-infected macaques. These results suggest that augmented Th17-type effector functions of CD161<sup>+</sup>CD8<sup>+</sup> T cells during SIV infection is a likely mechanism to compensate for the sustained loss of gut mucosal Th17 cells. Targeting the cytokine and cytolytic effector functions of CD161<sup>+</sup>CD8<sup>+</sup> T cells in the preclinical setting of chronic SIV infection with antiretroviral therapy has implications in the restoration of gut barrier disruption in persons with HIV infection.https://www.mdpi.com/1999-4915/15/9/1944mucosal immunityT cellsCD161SIVIL-17TNF-α |
| spellingShingle | Siva Thirugnanam Edith M. Walker Faith Schiro Pyone P. Aye Jay Rappaport Namita Rout Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques Viruses mucosal immunity T cells CD161 SIV IL-17 TNF-α |
| title | Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques |
| title_full | Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques |
| title_fullStr | Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques |
| title_full_unstemmed | Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques |
| title_short | Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161<sup>+</sup>CD8<sup>+</sup> T Cells in SIV-Infected Rhesus Macaques |
| title_sort | enhanced il 17 producing and maintained cytolytic effector functions of gut mucosal cd161 sup sup cd8 sup sup t cells in siv infected rhesus macaques |
| topic | mucosal immunity T cells CD161 SIV IL-17 TNF-α |
| url | https://www.mdpi.com/1999-4915/15/9/1944 |
| work_keys_str_mv | AT sivathirugnanam enhancedil17producingandmaintainedcytolyticeffectorfunctionsofgutmucosalcd161supsupcd8supsuptcellsinsivinfectedrhesusmacaques AT edithmwalker enhancedil17producingandmaintainedcytolyticeffectorfunctionsofgutmucosalcd161supsupcd8supsuptcellsinsivinfectedrhesusmacaques AT faithschiro enhancedil17producingandmaintainedcytolyticeffectorfunctionsofgutmucosalcd161supsupcd8supsuptcellsinsivinfectedrhesusmacaques AT pyonepaye enhancedil17producingandmaintainedcytolyticeffectorfunctionsofgutmucosalcd161supsupcd8supsuptcellsinsivinfectedrhesusmacaques AT jayrappaport enhancedil17producingandmaintainedcytolyticeffectorfunctionsofgutmucosalcd161supsupcd8supsuptcellsinsivinfectedrhesusmacaques AT namitarout enhancedil17producingandmaintainedcytolyticeffectorfunctionsofgutmucosalcd161supsupcd8supsuptcellsinsivinfectedrhesusmacaques |