T cells of different developmental stages differ in sensitivity to apoptosis induced by extracellular NAD

Friedrich Haag1, Dunja Freese, Felix Scheublein

  • 1Institute of Immunology, University Hospital, Martinistr. 52, D-20246 Hamburg, Germany. haag@uke.uni-hamburg.de

Insights

Extracellular nicotinamide adenine dinucleotide (NAD) induces T cell apoptosis, with sensitivity varying by developmental stage. This process may prevent unwanted T cell activation during immune responses and control autoimmunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Extracellular nucleotides like ATP and NAD modulate immune cell functions.
  • Extracellular NAD induces apoptosis in naive T cells via cell surface ADP-ribosylation.

Purpose of the Study:

  • To investigate differential sensitivity of T cells to NAD-induced apoptosis based on developmental stage and activation status.
  • To correlate NAD-induced apoptosis sensitivity with ADP-ribosyltransferase ART2.2 expression.

Main Methods:

  • Comparative analysis of T cell apoptosis induction by NAD across different developmental stages (thymocytes, peripheral T cells).
  • Assessment of T cell sensitivity to NAD-induced apoptosis in resting versus freshly activated states.
  • Quantification of ADP-ribosyltransferase ART2.2 expression on T cells.

Main Results:

  • Thymocytes exhibit lower susceptibility to NAD-induced apoptosis compared to peripheral T cells.
  • Freshly activated T cells are more resistant to NAD-induced apoptosis than resting T cells.
  • Sensitivity to NAD-induced apoptosis correlates with ART2.2 expression, which is absent on thymocytes and shed upon activation.

Conclusions:

  • NAD-induced apoptosis is unlikely to be involved in thymic T cell selection.
  • NAD-induced apoptosis may prevent bystander T cell activation during immune responses.
  • This mechanism could contribute to the control of autoimmunity.

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