| First Author | Miyakoda M | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 8 | Pages | 1319-1328 |
| PubMed ID | 29745988 | Mgi Jnum | J:274278 |
| Mgi Id | MGI:6196170 | Doi | 10.1002/eji.201747120 |
| Citation | Miyakoda M, et al. (2018) Differential requirements for IRF4 in the clonal expansion and homeostatic proliferation of naive and memory murine CD8(+) T cells. Eur J Immunol 48(8):1319-1328 |
| abstractText | Interferon regulatory factor 4 (IRF4) has critical roles in immune cell differentiation and function and is indispensable for clonal expansion and effector function in T cells. Here, we demonstrate that the AKT pathway is impaired in murine CD8(+) T cells lacking IRF4. The expression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT pathway, was elevated in Irf4(-/-) CD8(+) T cells. Inhibition of PTEN partially rescued downstream events, suggesting that PTEN constitutes a checkpoint in the IRF4-mediated regulation of cell signaling. Despite the clonal expansion defect, in the absence of IRF4, memory-like CD8(+) T cells could be generated and maintained, although unable to expand in recall responses. The homeostatic proliferation of naive Irf4(-/-) CD8(+) T cells was impaired, whereas their number eventually reached a level similar to that of wild-type CD8(+) T cells. Conversely, memory-like Irf4(-/-) CD8(+) T cells underwent homeostatic proliferation in a manner similar to that of wild-type memory CD8(+) T cells. These results suggest that IRF4 regulates the clonal expansion of CD8(+) T cells at least in part via the AKT signaling pathway. Moreover, IRF4 regulates the homeostatic proliferation of naive CD8(+) T cells, whereas the maintenance of memory CD8(+) T cells is IRF4-independent. |
