Effects of higher intracellular calcium amounts on T cell activation  

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B612
Abstract ID: 4403

Presenting Author:
Joel P Joseph , PhD student at Indian Inst. of Sci., Bangalore

Abstract:

Optimal activation of T cells is critical to orchestrate adaptive immune responses. Calcium is critical in T cell activation and integrates signaling pathways necessary to cause gene expression changes, culminating in T cell activation and proliferation. A previous report from our group demonstrated that 7-hydroxy-frullanolide inhibits T cell activation by increasing intracellular calcium levels. Here, we investigated the direct effects of high intracellular calcium levels on T cell activation using known compounds that increase intracellular calcium, Ionomycin and Thapsigargin. We found that high intracellular calcium levels inhibited T cell activation-associated proliferation as evidenced by a decreased cell cycling-to-hypodiploidy ratio in in vitro mouse T cell activation models: Phorbol 12-myristate 13-acetate and Ionomycin and plate bound anti-CD3 and anti-CD28. High intracellular calcium levels increased the production of reactive oxygen species (ROS), a possible mechanism by which high intracellular calcium inhibits T cell activation. Scavenging ROS using N-acetyl cysteine (NAC) rescued high calcium-induced decrease in T cell proliferation. Furthermore, we are investigating the effects of novel enhancers of intracellular calcium levels on inhibition of T cell activation in vitro and validating them in an in vivo mouse model of DSS-induced colitis. The observations will have implications in mechanistic understanding of T cell activation and treating autoimmune diseases.