@article {542051,
	title = {Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection.},
	journal = {J Exp Med},
	volume = {211},
	number = {9},
	year = {2014},
	month = {2014 Aug 25},
	pages = {1905-18},
	abstract = {Regulatory T (T reg) cells are critical for preventing autoimmunity mediated by self-reactive T cells, but their role in modulating immune responses during chronic viral infection is not well defined. To address this question and to investigate a role for T reg cells in exhaustion of virus-specific CD8 T cells, we depleted T reg cells in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). T reg cell ablation resulted in 10-100-fold expansion of functional LCMV-specific CD8 T cells. Rescue of exhausted CD8 T cells was dependent on cognate antigen, B7 costimulation, and conventional CD4 T cells. Despite the striking recovery of LCMV-specific CD8 T cell responses, T reg cell depletion failed to diminish viral load. Interestingly, T reg cell ablation triggered up-regulation of the molecule programmed cell death ligand-1 (PD-L1), which upon binding PD-1 on T cells delivers inhibitory signals. Increased PD-L1 expression was observed especially on LCMV-infected cells, and combining T reg cell depletion with PD-L1 blockade resulted in a significant reduction in viral titers, which was more pronounced than that upon PD-L1 blockade alone. These results suggest that T reg cells effectively maintain CD8 T cell exhaustion, but blockade of the PD-1 inhibitory pathway is critical for elimination of infected cells.},
	keywords = {Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Chronic Disease, Dendritic Cells, Lymphocyte Activation, Lymphocyte Depletion, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Mice, Transgenic, Programmed Cell Death 1 Receptor, T-Lymphocytes, Regulatory, Up-Regulation},
	issn = {1540-9538},
	doi = {10.1084/jem.20132577},
	author = {Penaloza-MacMaster, Pablo and Kamphorst, Alice O and Wieland, Andreas and Araki, Koichi and Iyer, Smita S and West, Erin E and O{\textquoteright}Mara, Leigh and Yang, Shu and Konieczny, Bogumila T and Sharpe, Arlene H and Freeman, Gordon J and Rudensky, Alexander Y and Ahmed, Rafi}
}
