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
Abstract:
Extracellular nucleotides such as ATP and NAD can profoundly affect the functions of lymphocytes, macrophages, and other cells. We have recently shown that extracellular NAD induces rapid apoptosis in naive T cells by a mechanism involving the ADP-ribosylation of cell surface molecules. In the present paper, we describe that T cells of different developmental stages differ in their sensitivity to NAD-induced apoptosis. Thymocytes were less susceptible than peripheral lymph node T cells, and freshly activated cells were more resistant than resting cells. Sensitivity to NAD-induced apoptosis generally correlated with expression of the ADP-ribosyltransferase ART2.2, which is not expressed on thymocytes and shed from peripheral T cells upon activation. Our findings suggest that NAD-induced apoptosis does not play a role during thymic selection of T cells, but rather may play a role by preventing the activation of unwanted bystander T cells during an immune response, and thus may participate in the control of autoimmunity.
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.
More Related Videos
Related Concept Videos
Apoptosis
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cellular Injury V: Apoptosis and Autophagy


