The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8 + Memory T Cell Maintenance and Secondary Response to Infection

J Immunol. 2019 Jul 1;203(1):117-126. doi: 10.4049/jimmunol.1801585. Epub 2019 May 24.

Abstract

Access to nutrients is critical for an effective T cell immune response to infection. Although transporters for sugars and amino acids have previously been described in the context of the CD8+ T cell immune response, the active transport of exogenous fatty acids has remained enigmatic. In this study, we discovered that the sodium-dependent lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (MFSD2A) is upregulated on activated CD8+ T cells and is required for memory T cell maintenance. MFSD2A deficiency in mice resulted in decreased import of LPC esterified to long chain fatty acids into activated CD8+ T cells, and MFSD2A-deficient cells are at a competitive disadvantage resulting in reduced memory T cell formation and maintenance and reduced response to secondary infection. Mechanistically, import of LPCs was required to maintain T cell homeostatic turnover, which when lost resulted in a decreased memory T cell pool and thus a reduced secondary response to repeat infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Homeostasis
  • Immunologic Memory
  • Listeria / genetics
  • Listeria / physiology*
  • Listeriosis / immunology*
  • Lymphocyte Activation
  • Lysophosphatidylcholines / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Symporters / genetics
  • Symporters / metabolism*
  • Up-Regulation

Substances

  • Lysophosphatidylcholines
  • Mfsd2a protein, mouse
  • Symporters
  • Ovalbumin