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Ryan Webb, Matlock Jeffries, Amr H Sawalha, The DNA degradation product uric acid directly promotes T cell autoreactivity (90.1), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S156, https://doi.org/10.4049/jimmunol.178.Supp.90.1
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Abstract
Purpose: Abnormally high serum uric acid levels have been associated with several disease conditions including gout and kidney stone disease. More recently, it was shown that uric acid crystals stimulate dendritic cell maturation, activate the NALP3 inflammasome, and enhance antigen-specific immune response. We hypothesize that uric acid can also stimulate T cells directly and in the absence of antigen presentation.
Methods: Purified primary human T cells were incubated with and without uric acid at concentrations of 50, 100, 150 and 200 μg/ml. This range of uric acid concentrations covers the normal physiologic serum uric acid concentration as well as a spectrum of hyperuricemic values in human. The expression of T cell activation markers CD25 and CD70 was assessed by flow cytometry. Purified human T cell proliferation response to the various uric acid concentrations was quantified using a colorimetric proliferation assay.
Results: Uric acid treatment resulted in antigen-independent T cell activation as determined by increased expression of CD25 in both CD4+ as well as CD8+ T cells. CD4+ T cells also overexpressed CD70, a co-stimulation molecule important in T cell-dependent B cell activation. In addition, we demonstrate a dose response relationship between T cell proliferation and uric acid concentration in vitro.
Conclusion: The finding that uric acid directly promotes T cell proliferation and activation in an antigen-independent system is novel and might play a mechanistic role in the inflammatory response observed in gout and other uric acid associated diseases.
This work is supported by NIH Grant Number P20-RR015577 and the University of Oklahoma Health Sciences Center.
