The Role of Zap70 Activity in T-cell Proliferation and Function

Because T-cells play a large role in the autoimmune response, defining the mechanism and timing of T-cell activation is critical to understanding and treating autoimmune diseases.Zap70 is a cytoplasmic tyrosine kinase involved in the T-cell receptor signaling pathway. Our lab developed a genetically selective Zap70 inhibitor system to study Zap70’s role in T-cells. We stimulated CD4+ T-cells in the presence of varying concentrations of inhibitor, added at 0, 24, or 48 hours. Cells that were given a high dose of inhibitor at 0 hours showed minimal proliferation, while cells that received a DMSO control showed the ability to undergo division up to five times. T-cells given a high dose of inhibitor at 48 hours were still able to undergo up to five divisions. Overall, the results demonstrate proliferation that is time and inhibitor-dose dependent.