| First Author | Brzostek J | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 2 | Pages | 186-198 |
| PubMed ID | 31932808 | Mgi Jnum | J:290690 |
| Mgi Id | MGI:6436233 | Doi | 10.1038/s41590-019-0570-3 |
| Citation | Brzostek J, et al. (2020) T cell receptor and cytokine signal integration in CD8(+) T cells is mediated by the protein Themis. Nat Immunol 21(2):186-198 |
| abstractText | T cell homeostasis and functional responsiveness require signals from self-peptide-major histocompatibility complex (self-pMHC) and cytokines, but the mechanisms controlling this signal integration are unknown. Using a conditional deletion of the T cell lineage-specific protein Themis, we show that Themis is required for the maintenance of peripheral CD8(+) T cells and for proliferative CD8(+) T cell responses to low-affinity pMHC aided by cytokines. Themis-deficient peripheral T cells show a phenotype indicative of reduced tonic signaling from self-pMHC, strongly suggesting that Themis is a positive regulator of T cell receptor signal strength in response to low-affinity self-pMHC in peripheral T cells. Signals from low-affinity pMHC and cytokines synergistically induce phosphorylation of the kinase Akt, metabolic changes and c-Myc transcription factor induction in CD8(+) T cells only in the presence of Themis. This function of Themis is mediated through Shp1 phosphatase, as peripheral Themis and Shp1 double deletion rescues the peripheral CD8(+) T cell maintenance. |
