The lysophosphatidylcholine transporter, MFSD2A, is essential for CD8+ memory T cell maintenance and secondary response to infection

Abstract

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. Here we discovered the sodium-dependent lysophosphatidylcholine transporter, Major Facilitator Super Family 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 lysophosphatidylcholine (LPC) esterified to long chain fatty acids (LCFAs) 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, that when lost resulted in a decreased memory T cell pool and thus a reduced secondary response to repeat infection.