RETRACTED: The protein LEM promotes CD8 + T cell immunity through effects on mitochondrial respiration

During an infection, T cells proliferate extensively to build a sufficient army to defeat the invading pathogen. Carefully regulated changes in metabolism let T cells do this, but the specific nature of these changes is not fully understood. Using forward genetics in mice to screen for genes that regulate T cell immunity, Okoye et al. identified a mutation in the gene that encodes a protein they named lymphocyte expansion molecule (LEM) (see the Perspective by O'Sullivan and Pearce). LEM enhanced T cell immunity, including both proliferation and memory cell generation, in response to chronic viral infection. LEM facilitated these changes through effects on mitochondrial respiration. Science , this issue p. 995 ; see also p. 976 Forward genetics identifies a protein that promotes T cell immunity by affecting metabolism. [Also see Perspective by O'Sullivan and Pearce ] Protective CD8 + T cell–mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8 + T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8 + T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8 + T cells.