Proc. Natl Acad. Sci. USA (2020)

Many pathogens can infect the thymus and thereby potentially disrupt the education and development of thymocytes. In the Proceedings of the National Academy of Sciences of the USA, Brooks and colleagues use a chronic lymphocytic choriomeningitis virus (LCMV) model to investigate the long-term consequences of infection on the T cell compartment. Following infection, LCMV is readily detectable in the thymus, primarily infecting hematopoietic cells and especially medullary dendritic cells. LCMV infection results in involution of the thymus and a dramatic reduction in double-positive thymocytes. This thymic disruption and the loss of thymocytes are dependent on the recruitment of LCMV-specific CD8+ T cells and a largely T cell–intrinsic interferon-α–STAT2 signaling pathway. Surprisingly, the continued presence of LCMV in the thymus doesn’t result in negative selection of LCMV-specific thymocytes; rather, there appears to be a compensatory reduction in negative selection, allowing rescue of these useful clones, but at the cost of the escape of potentially hazardous autoreactive T cells.