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Protein Kinase C-η Deficiency Does Not Impair Antiviral Immunity and CD8
- Source :
- J Immunol
- Publication Year :
- 2019
-
Abstract
- We reported that protein kinase C-eta (PKCη) forms a novel 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 anti-tumor immunity. However, the importance of PKCη in protective immunity mediated by T effector (Teff) cells remains unclear. We used mice with germline or conditional, Treg-specific deletion of Prkch, the PKCη-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 to control mice. Similarly, Prkch Treg-specific conditional knockout (cKO) mice also showed improved viral clearance and displayed enhanced expression of granzyme B (GzmB) and interferon-γ (IFNγ) by both virus-specific and total CD8(+) T cells, demonstrating that enhanced viral clearance in germline Prkch(−/−) mice is caused by PKCη 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 GzmB and IFNγ. Thus, global PKCη deletion does not impair overall CD8(+) T cell-mediated immunity, including antiviral immunity, implying that selective pharmacological PKCη 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.
- Subjects :
- Mice, Knockout
Immunity, Cellular
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Antiviral Agents
T-Lymphocytes, Regulatory
Granzymes
Article
Cell Line
Interferon-gamma
Mice
HEK293 Cells
Animals
Humans
Lymphocytic choriomeningitis virus
CTLA-4 Antigen
Protein Kinase Inhibitors
Protein Kinase C
Cell Proliferation
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 204
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.pmid..........b5adf935e5b81d7a4cc9791b6f6f690b