Glycosylphosphatidylinositol (GPI)-deficient Jurkat T cells as a model to study functions of GPI-anchored proteins

Many cell surface proteins attached to the membrane by GPI are involved in cell signalling. However, the role of the GPI membrane anchor itself remain s poorly understood. GPI-defective cells from patients with paroxysmal noct urnal haemoglobinuria (PNH) are relatively resistant to apoptosis induction . We developed a Jurkat T cell model for GPI deficiency by isolating a GPI- negative mutant, which is defective in the GPI biosynthetic gene PIG-A. Usi ng retroviral PIG-A gene transfer along with the transfer of a vector contr ol, we obtained two genetically identical cell Lines, distinguished only by expression of the PIG-A gene and, thus, their ability to produce GPI. Cell proliferation and survival were not affected by this difference. Apoptotic stimuli such as serum starvation and camptothecin exposure elicited simila r responses. In contrast, GPI-defective Jurkat cells were more susceptible to Fas-mediated apoptosis than GPI-positive cells. These results indicate t hat a deficiency in GPI-anchored proteins, as is found in PNH, does not con fer resistance to apoptosis.