| First Author | Liu HY | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 9 | Pages | 2439-2446 |
| PubMed ID | 32198145 | Mgi Jnum | J:288527 |
| Mgi Id | MGI:6432157 | Doi | 10.4049/jimmunol.1900963 |
| Citation | Liu HY, et al. (2020) Protein Kinase C-eta Deficiency Does Not Impair Antiviral Immunity and CD8(+) T Cell Activation. J Immunol 204(9):2439-2446 |
| abstractText | We reported that protein kinase C-eta (PKCeta) forms a novel (to our knowledge) signaling complex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs). This complex is required for the contact-dependent suppressive activity of Tregs, including suppression of antitumor immunity. However, the importance of PKCeta in protective immunity mediated by T effector cells remains unclear. We used mice with germline or conditional Treg-specific deletion of Prkch, the PKCeta-encoding gene, to explore CD8(+) T cell-dependent antiviral immunity using the lymphocytic choriomeningitis virus Armstrong strain acute infection model as well as the in vitro activation of murine or human CD8(+) T cells. Five days following infection, germline Prkch (-/-) mice displayed enhanced viral clearance compared with control mice. Similarly, Prkch Treg-specific conditional knockout mice also showed improved viral clearance and displayed enhanced expression of granzyme B and IFN-gamma by both virus-specific and total CD8(+) T cells, demonstrating that enhanced viral clearance in germline Prkch (-/-) mice is caused by PKCeta deficiency in Tregs and the resulting functional defect of Prkch (-/-) Tregs. In addition, purified Prkch (-/-) mouse CD8(+) T cells as well as PRKCH knockdown human CD8(+) T cells displayed intact, or even enhanced, T cell activation in vitro as measured by proliferation and expression of granzyme B and IFN-gamma. Thus, global PKCeta deletion does not impair overall CD8(+) T cell-mediated immunity, including antiviral immunity, implying that selective pharmacological PKCeta inhibition could be safely used in vivo to inhibit undesired contact-dependent suppression by Tregs and, thus, enhance tumor-specific and, likely, virus-specific immunity. |
