Functional impairment of CD8 T cells following acute virus infections (43.32)

Abstract

Abstract Following acute respiratory syncytial virus (RSV) infection the virus-specific CD8 T cells from the spleen show a 1:1 correspondence between tetramer staining and in vitro cytokine production after peptide stimulation. In contrast, pulmonary virus-specific CD8 T cells are deficient in IFN-γ and TNF-α production and show impaired ex vivo cytotoxicity compared to CD8 T cells from the spleen. We have studied CD8 T cell functional impairment in viral infections outside the Paramyxoviridae family and show that similar dysregulation of pulmonary CD8 T cells also occurs after respiratory infections by lymphocytic choriomeningitis virus (LCMV) and by vaccinia virus expressing the RSV M2 protein (vvM2). In addition, LCMV and vvM2-specific CD8 T cells in the lungs demonstrate impaired degranulation relative to splenic CD8 T cells as measured by CD107a staining following ex vivo peptide stimulation. Importantly, we show here that pulmonary CD8 T cell IFN-γ and TNF-α production can be recovered by stimulating these cells in vitro using P815 cells pulsed with peptide as a source of exogenous antigen presenting cells (APCs). Our results indicate that the CD8 T cells in the lung are fully functional and that the apparent functional impairment may be caused by the APC milieu within the lung tissue.