CD44 regulates survival and memory development in Th1 cells

Immunity. 2010 Jan 29;32(1):104-15. doi: 10.1016/j.immuni.2009.10.011. Epub 2010 Jan 14.

Abstract

Optimal immunity to microorganisms depends upon the regulated death of clonally expanded effector cells and the survival of a cohort of cells that become memory cells. After activation of naive T cells, CD44, a widely expressed receptor for extracellular matrix components, is upregulated. High expression of CD44 remains on memory cells and despite its wide usage as a "memory marker," its function is unknown. Here we report that CD44 was essential for the generation of memory T helper 1 (Th1) cells by promoting effector cell survival. This dependency was not found in Th2, Th17, or CD8(+) T cells despite similar expression of CD44 and the absence of splice variants in all subsets. CD44 limited Fas-mediated death in Th1 cells and its ligation engaged the phosphoinositide 3-kinase-Akt kinase signaling pathway that regulates cell survival. The difference in CD44-regulated apoptosis resistance in T cell subpopulations has important implications in a broad spectrum of diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Hyaluronan Receptors / immunology*
  • Hyaluronan Receptors / metabolism
  • Immunoblotting
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism

Substances

  • Hyaluronan Receptors