Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4 + T Cells

Academic Article

Abstract

  • Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed by CD4 + T cells and tempers their homeostatic expansion. Because CD4 + T cell proliferation is tightly coupled to bioenergetics, we investigate the role of LAG-3 in modulating naive CD4 + T cell metabolism. LAG-3 deficiency enhances the metabolic profile of naive CD4 + T cells by elevating levels of mitochondrial biogenesis. In vivo, LAG-3 blockade partially restores expansion and the metabolic phenotype of wild-type CD4 + T cells to levels of Lag3 −/− CD4 + T cells, solidifying that LAG-3 controls these processes. Lag3 −/− CD4 + T cells also demonstrate greater signal transducer and activator of transcription 5 (STAT5) activation, enabling resistance to interleukin-7 (IL-7) deprivation. These results implicate this pathway as a target of LAG-3-mediated inhibition. Additionally, enhancement of STAT5 activation, as a result of LAG-3 deficiency, contributes to greater activation potential in these cells. These results identify an additional mode of regulation elicited by LAG-3 in controlling CD4 + T cell responses. Previte et al. show that LAG-3 expression regulates the metabolic profile of naive CD4 + T cells during homeostatic expansion. They observed that Lag3-deficient CD4 + T cells are resistant to Interleukin-7 deprivation due to enhanced STAT5 activation. Increased STAT5 signaling also mediated greater activation potential in these T cells following stimulation.
  • Authors

    Published In

  • Cell Reports  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 20549686
  • Author List

  • Previte DM; Martins CP; O'Connor EC; Marre ML; Coudriet GM; Beck NW; Menk AV; Wright RH; Tse HM; Delgoffe GM
  • Start Page

  • 129
  • End Page

  • 141.e4
  • Volume

  • 27
  • Issue

  • 1