First Author | Murera D | Year | 2018 |
Journal | Sci Rep | Volume | 8 |
Issue | 1 | Pages | 5951 |
PubMed ID | 29654322 | Mgi Jnum | J:262624 |
Mgi Id | MGI:6163152 | Doi | 10.1038/s41598-018-23993-0 |
Citation | Murera D, et al. (2018) CD4 T cell autophagy is integral to memory maintenance. Sci Rep 8(1):5951 |
abstractText | Studies of mice deficient for autophagy in T cells since thymic development, concluded that autophagy is integral to mature T cell homeostasis. Basal survival and functional impairments in vivo, limited the use of these models to delineate the role of autophagy during the immune response. We generated Atg5 (f/f) distal Lck (dLck)-cre mice, with deletion of autophagy only at a mature stage. In this model, autophagy deficiency impacts CD8(+) T cell survival but has no influence on CD4(+) T cell number and short-term activation. Moreover, autophagy in T cells is dispensable during early humoral response but critical for long-term antibody production. Autophagy in CD4(+) T cells is required to transfer humoral memory as shown by injection of antigen-experienced cells in naive mice. We also observed a selection of autophagy-competent cells in the CD4(+) T cell memory compartment. We performed in vitro differentiation of memory CD4(+) T cells, to better characterize autophagy-deficient memory cells. We identified mitochondrial and lipid load defects in differentiated memory CD4(+) T cells, together with a compromised survival, without any collapse of energy production. We then propose that memory CD4(+) T cells rely on autophagy for their survival to regulate toxic effects of mitochondrial activity and lipid overload. |