Effects of Arsenic Ingestion on Antiviral T Cell Responses

Richard I. Enelow, M.D.
Bruce A. Stanton, Ph.D.

This pilot study will build on an interesting set of observations in murine influenza, after treatment with 100 ppb Arsenic (As) in their drinking water, which showed that As-treated infected animals have a delay in influenza virus clearance compared to untreated infected mice. Of particular interest, the T cell responses in the lung were significantly delayed, though considerably more robust infiltration than in the lungs of untreated mice. Though the exploratory data suggested a defect in antigen presentation by dendritic cells, there have been no explorations into the functions and activities of the antiviral T cells (essential for clearance), the degree to which their effector activities were either impaired (allowing prolonged viral clearance) or dysregulated (resulting in greater injury to the airways). This pilot study is designed to test the hypothesis that ingestion of 100 ppb arsenic prior to infection impairs the activation and expansion of CD8+ T cells in response to influenza infection, as well as the hypothesis that ingestion of 100 ppb arsenic prior to infection impairs the downregulation and contraction of CD8+ T cells during clearance of influenza infection. We have previously shown that the magnitude of the inflammatory infiltration, while delayed, is greater in As-treated versus untreated controls after sub-lethal influenza infection. We want to characterize the programmed expression of pro-apoptotic mediators expressed by antiviral T cells upon activation.