T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell homeostasis

Immunity. 2010 Feb 26;32(2):214-26. doi: 10.1016/j.immuni.2009.11.014. Epub 2010 Feb 4.


T cell receptor (TCR) contact with self ligands keeps T cells alive and is shown here to cause naive CD8(+), but not CD4(+), T cells to be hypersensitive to certain gamma(c) cytokines, notably interleukin (IL)-2, IL-15, and IL-7. Hypersensitivity of CD8(+) T cells to IL-2 was dependent on a low-level TCR signal, associated with high expression of CD5 and GM1, a marker for lipid rafts, and was abolished by disruption of lipid rafts. By contrast, CD4(+) T cells expressed low amounts of GM1 and were unresponsive to IL-2. Physiologically, sensitivity to IL-7 and IL-15 maintains survival of resting CD8(+) T cells, whereas sensitivity to IL-2 may be irrelevant for normal homeostasis but crucial for the immune response. Thus, TCR contact with antigen upregulates GM1 and amplifies responsiveness of naive CD8(+) T cells to IL-2, thereby making the cells highly sensitive to exogenous IL-2 from CD4(+) T helper cells.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Survival / immunology
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Glycosphingolipids / biosynthesis*
  • Glycosphingolipids / genetics
  • Glycosphingolipids / immunology
  • Histocompatibility Antigens / metabolism
  • Homeostasis
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Membrane Microdomains / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology


  • Autoantigens
  • Cytokines
  • Glycosphingolipids
  • Histocompatibility Antigens
  • Interleukin Receptor Common gamma Subunit
  • Peptide Fragments
  • Receptors, Antigen, T-Cell