Abstract
Activation induced cell death (AICD) of T lymphocytes plays a vital role in the regulation of the immune response. Cellular resistance to apoptosis can contribute to cancer and autoimmune diseases. Vasoactive intestinal peptide receptor 1 and 2 (VPAC1/2) are G‐protein coupled receptors highly expressed in the immune system that bind vasoactive intestinal peptide (VIP). It has been previously shown that inducible VPAC2 inhibits apoptosis in Th2 polarized CD4 T cells. However, the effect of VPAC1 signaling is not well understood. Naïve and activated HuT 78 cells, a transformed human T lymphocyte cell line predominantly expressing VPAC1, were treated +/‐ VIP. The extent of apoptosis was measured using a histone fragmentation‐based ELISA. In activated cells, VIP had little effect on apoptosis (10‐6‐10‐10M), but caused a significant increase in apoptosis in naïve cells (10‐8M). VIP/VPAC1 signaling induces apoptosis in naïve T cells but has little effect on activated cells. Furthermore, it appears that the VPAC1 and VPAC2 receptors affect apoptosis in opposing ways, most likely due to subtle differences in intracellular signaling. Research supported by NIH‐K01 1K01DK064828 and COBRE 2P20RR05566.
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