Disruption of positive selection of thymocytes causes autoimmunity
Anke Kretz-Rommel
& Robert L. Rubin
W.M. Keck Autoimmune Disease Center, Department of
Molecular and Experimental Medicine, The Scripps Research Institute,
MEM 131, 10550 North Torrey Pines Road, La Jolla,
California 92037, USA
Correspondence should be addressed to Robert L. Rubin rrubin@scripps.edu
To differentiate into T cells, immature thymocytes must engage, through
their antigen-specific T-cell receptor, peptides derived from self proteins
presented by cortical epithelial cells in the thymus, a process called positive
selection. Despite this requirement for self-recognition during development,
mature T cells do not normally show autoreactivity. Mice injected in the thymus
with procainamide-hydroxylamine, a metabolite of procainamide, develop autoimmune
features resembling drug-induced lupus. Here, we show that when thymocytes
undergo positive selection in the presence of procainamide-hydroxylamine,
they fail to establish unresponsiveness to low affinity selecting self antigens,
resulting in systemic autoimmunity.
