Submitted May 21, 2008
Accepted December 28, 2008
Complement-dependent T cell lymphopenia caused by thymocyte deletion of the membrane complement regulator Crry
Takashi Miwa, Lin Zhou, Yuko Kimura, David Kim, Avinash Bhandoola, and Wen-Chao Song*
Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
* Corresponding author; email: song{at}spirit.gcrc.upenn.edu.
Although complement lysis is frequently used for the purification of lymphocyte subpopulations in vitro, how lymphocytes escape complement attack in vivo has not been clearly delineated. Here, we show that conditional gene targeting of a murine membrane complement regulator Crry on thymocytes led to complement-dependent peripheral T cell lymphopenia. Notably, despite evidence of hypersensitivity to complement attack, Crry-deficient T cells escaped complement injury and developed normally in the thymus, owing to low intrathymic complement activity. Crry-deficient T cells were eliminated in the periphery by a C3- and macrophage-mediated but C5-independent mechanism. Thus, Crry is essential for mature T cell survival in the periphery but not for lymphogenesis in the thymus. The observation that the thymus is a complement-privileged site may have implications for complement-based anti-tumor therapies.
