| First Author | Shehata HM | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 38 | Pages | E8939-E8947 |
| PubMed ID | 30126987 | Mgi Jnum | J:265930 |
| Mgi Id | MGI:6200185 | Doi | 10.1073/pnas.1808320115 |
| Citation | Shehata HM, et al. (2018) Lack of Sprouty 1 and 2 enhances survival of effector CD8(+) T cells and yields more protective memory cells. Proc Natl Acad Sci U S A 115(38):E8939-E8947 |
| abstractText | Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer and chronic infections. We show that sprouty 1 and 2 (Spry1/2) molecules regulate the survival and function of memory CD8(+) T cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific CD8(+) T cells (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I cells when transferred to mice expressing OVA in their pancreatic beta-islets. To determine the consequence of Spry1/2 deletion on effector and memory CD8(+) T cell development and function, we used systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong. Spry1/2 DKO LCMV gp33-specific P14 CD8(+) T cells survive contraction better than WT cells and generate significantly more polyfunctional memory T cells. The larger number of Spry1/2 DKO memory T cells displayed enhanced infiltration into infected tissue, demonstrating that absence of Spry1/2 can result in increased recall capacity. Upon adoptive transfer into naive hosts, Spry1/2 DKO memory T cells controlled Listeria monocytogenes infection better than WT cells. The enhanced formation of more functional Spry1/2 DKO memory T cells was associated with significantly reduced mTORC1 activity and glucose uptake. Reduced p-AKT, p-FoxO1/3a, and T-bet expression was also consistent with enhanced survival and memory accrual. Collectively, loss of Spry1/2 enhances the survival of effector CD8(+) T cells and results in the formation of more protective memory cells. Deleting Spry1/2 in antigen-specific CD8(+) T cells may have therapeutic potential for enhancing the survival and functionality of effector and memory CD8(+) T cells in vivo. |
