The Requirement of Reversible Cysteine Sulfenic Acid Formation in T Cell Activation and Function (87.40)

Abstract

Abstract Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in mediating cellular responses. We have examined the importance of reversible cysteine sulfenic acid formation in naïve CD8+ T cell activation and proliferation. We observed that within minutes of T cell activation, naïve CD8+ T cells increased ROI levels in a manner dependent upon antigen concentration. With increased ROI, levels of cysteine sulfenic acid were also elevated. To examine the contribution of reversible cysteine sulfenic acid formation to T cell activation increasing concentrations of 5, 5 dimethyl-1,3-cyclohexanedione (dimedone), which covalently binds to cysteine sulfenic acid, were added to cultures. Subsequent experiments demonstrated that the reversible formation of cysteine sulfenic acid was critical for ERK1/2 phosphorylation, calcium flux, cell growth, proliferation, and cytokine production of naïve CD8+ and CD4+ T cells. We also found that TNF-α production by effector and memory CD8+ T cells was more sensitive to inhibition of reversible cysteine sulfenic acid formation than IFN-γ. Together, these results demonstrate that reversible cysteine sulfenic acid formation is an important regulatory mechanism by which CD8+ T cells are able to modulate signaling, proliferation, and function. Research supported by American Cancer Society- #RSG-04-066-01-MBC to Jason Grayson.