| First Author | Tzelepis F | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 3 | Pages | 1066-75 |
| PubMed ID | 23277488 | Mgi Jnum | J:193028 |
| Mgi Id | MGI:5467439 | Doi | 10.4049/jimmunol.1200639 |
| Citation | Tzelepis F, et al. (2013) Intrinsic role of FoxO3a in the development of CD8+ T cell memory. J Immunol 190(3):1066-75 |
| abstractText | CD8(+) T cells undergo rapid expansion during infection with intracellular pathogens, which is followed by swift and massive culling of primed CD8(+) T cells. The mechanisms that govern the massive contraction and maintenance of primed CD8(+) T cells are not clear. We show in this study that the transcription factor, FoxO3a, does not influence Ag presentation and the consequent expansion of CD8(+) T cell response during Listeria monocytogenes infection, but plays a key role in the maintenance of memory CD8(+) T cells. The effector function of primed CD8(+) T cells as revealed by cytokine secretion and CD107a degranulation was not influenced by inactivation of FoxO3a. Interestingly, FoxO3a-deficient CD8(+) T cells displayed reduced expression of proapoptotic molecules BIM and PUMA during the various phases of response, and underwent reduced apoptosis in comparison with wild-type cells. A higher number of memory precursor effector cells and memory subsets was detectable in FoxO3a-deficient mice compared with wild-type mice. Furthermore, FoxO3a-deficient memory CD8(+) T cells upon transfer into normal or RAG1-deficient mice displayed enhanced survival. These results suggest that FoxO3a acts in a cell-intrinsic manner to regulate the survival of primed CD8(+) T cells. |
