The CD28 signaling pathway regulates glucose metabolism

Immunity. 2002 Jun;16(6):769-77. doi: 10.1016/s1074-7613(02)00323-0.


Lymphocyte activation initiates a program of cell growth, proliferation, and differentiation that increases metabolic demand. Although T cells increase glucose uptake and glycolysis during an immune response, the signaling pathways that regulate these increases remain largely unknown. Here we show that CD28 costimulation, acting through phosphatidylinositol 3'-kinase (PI3K) and Akt, is required for T cells to increase their glycolytic rate in response to activation. Furthermore, CD28 controls a primary response pathway, inducing a level of glucose uptake and glycolysis in excess of that needed to maintain cellular ATP/ADP levels or macromolecular synthesis. These data suggest that CD28 costimulation functions to increase glycolytic flux, allowing T cells to anticipate energetic and biosynthetic needs associated with a sustained response.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Binding Sites
  • CD28 Antigens / physiology*
  • Cell Line
  • Glucose / metabolism*
  • Glucose Transporter Type 1
  • Glycolysis
  • Homeostasis
  • Humans
  • Lymphocyte Activation
  • Monosaccharide Transport Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases*
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction*
  • Spectrometry, Fluorescence


  • CD28 Antigens
  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins
  • Proto-Oncogene Proteins
  • SLC2A1 protein, human
  • Adenosine Diphosphate
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Glucose