Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes. A potential role for the acidic sphingomyelinase pathway in normal immunoregulation

J Clin Invest. 1996 Jan 15;97(2):316-22. doi: 10.1172/JCI118418.


The expression and function of Fas (CD95/APO-1), a cell surface receptor directly responsible for triggering cell death by apoptosis, was investigated on human T lymphocytes resident within the intestinal lamina propria, a major site of antigen challenge and persistent lymphocyte activation. Three color immunofluorescence and FACS analysis indicated that virtually all freshly isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together with the marker of progress activation CD45R0. A discrete fraction of freshly isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a result of recent in vivo activation. Importantly, whereas Fas cross-linking did not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas was found to be fully effective in generating the apoptotic signal in T-LPL. This was associated with the activation of an acidic sphingomyelinase and with ceramide generation, early events known to be involved in Fas-mediated apoptotic signaling. By contrast, acidic sphingomyelinase activation and ceramide production were not detectable in T-PBL after Fas cross-linking. However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T-LPL constitutively express both Fas and FasL and that Fas cross-linking generates signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a potential mechanism involved in intestinal tolerance. Moreover, they provide the first evidence of a role for ceramide-mediated pathways in normal immunoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Ceramides / pharmacology
  • Fas Ligand Protein
  • Flow Cytometry
  • Humans
  • Immunity, Mucosal*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Leukocyte Common Antigens / metabolism
  • Membrane Glycoproteins / metabolism*
  • Sphingomyelin Phosphodiesterase / physiology*
  • Sphingomyelins / metabolism
  • T-Lymphocytes / metabolism*
  • fas Receptor / metabolism*


  • Ceramides
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Sphingomyelins
  • fas Receptor
  • Leukocyte Common Antigens
  • Sphingomyelin Phosphodiesterase