Key role of T cell defects in age-related vulnerability to West Nile virus

• DOI: 10.1084/jem.20090222
• Publication Date: 2009-11-10T03:06:01Z
• Authors: James D. Brien; Jennifer L. Uhrlaub; Alec Hirsch; Clayton A. Wiley; Janko Nikolich-Žu...
• Keywords: Adoptive Cell Transfer

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40–50× in people 70, compared with adults under 40. In mouse model age-related vulnerability to WNV, we demonstrate death correlates increased viral titers brain this loss control was result defects CD4 CD8 T cell response against WNV. Specific responses dominant WNV epitopes were detected at level cytokine lytic granule production, each which are essential for resistance ability generate multifunctional anti-WNV effector cells, believed be critical robust antiviral immunity. contrast, peak response, old adult cells exhibited superimposable peptide sensitivity. Most importantly, although or readily protected immunodeficient mice upon adoptive transfer, either subset unable provide WNV-specific protection. Consistent profound qualitative quantitative defect immunity, brains contained least 12× fewer total infection. These findings identify potential targets immunomodulation treatment combat lethal elderly.