High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival

• DOI: 10.1084/jem.20150598
• Publication Date: 2016-07-25T14:12:22Z
• Authors: Daniel T. Utzschn...; Francesca Alfei; Patrick Roelli; David Barras; Vijaykumar Chennu...; Stephanie Darbre; Mauro Delorenzi; Daniel D. Pinschewer; Dietmar Zehn
• Keywords: Chronic infection

Chronic infections induce T cells showing impaired cytokine secretion and up-regulated expression of inhibitory receptors such as PD-1. What determines the acquisition this chronic phenotype how it impacts cell function remain vaguely understood. Using newly generated recombinant antigen variant-expressing lymphocytic choriomeningitis virus (LCMV) strains, we uncovered that differentiation a or exhausted depend critically on frequency receptor (TCR) engagement less significantly strength TCR stimulation. In fact, noted low-level exposure promotes formation with an acute in infections. Unexpectedly, found populations are maintained equally well undergo comparable primary secondary expansion. Thus, our observations contrast view typical infection severely functionally rapidly transition into terminal stage differentiation. Instead, data unravel primarily form phenotypic functional early phase LCMV without inheriting net survival expansion deficit, demonstrate acquired transitions memory compartment.