Canonical Wnts Mediate CD8+ T Cell Noncytolytic Anti–HIV-1 Activity and Correlate with HIV-1 Clinical Status
| Autor: | Lena Al-Harthi, Beverly E. Sha, Srinivas D. Narasipura, Jennillee Wallace, Audrey L. French |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
T cell
Immunology Wnt signaling pathway virus diseases Biology In vitro 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Mediator Downregulation and upregulation Transcription (biology) medicine Cancer research Immunology and Allergy Cytotoxic T cell CD8 030215 immunology |
| Zdroj: | The Journal of Immunology. 205:2046-2055 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1801379 |
| Popis: | CD8+ T cells do not rely solely on cytotoxic functions for significant HIV control. Moreover, the noncytotoxic CD8+ T cell antiviral response is a primary mediator of natural HIV control such as that seen in HIV elite controllers and long-term nonprogressors that does not require combined antiretroviral therapy. In this study, we investigated the biological factors contributing to the noncytotoxic control of HIV replication mediated by primary human CD8+ T cells. We report that canonical Wnt signaling inhibits HIV transcription in an MHC-independent, noncytotoxic manner and that mediators of this pathway correlate with HIV controller clinical status. We show that CD8+ T cells express all 19 Wnts and CD8+ T cell–conditioned medium (CM) induced canonical Wnt signaling in infected recipient cells while simultaneously inhibiting HIV transcription. Antagonizing canonical Wnt activity in CD8+ T cell CM resulted in increased HIV transcription in infected cells. Further, Wnt2b expression was upregulated in HIV controllers versus viremic patients, and in vitro depletion of Wnt2b and/or Wnt9b from CD8+ CM reversed HIV inhibitory activity. Finally, plasma concentration of Dkk-1, an antagonist of canonical Wnt signaling, was higher in viremic patients with lower CD4 counts. This study demonstrates that canonical Wnt signaling inhibits HIV and significantly correlates with HIV controller status. |
| Databáze: | OpenAIRE |
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