Complement-dependent T-cell lymphopenia caused by thymocyte deletion of the membrane complement regulator Crry.
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, because of 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 antitumor therapies.
Miwa
Takashi
T
Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Zhou
Lin
L
Kimura
Yuko
Y
Kim
David
D
Bhandoola
Avinash
A
Song
Wen-Chao
WC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D017637:Clonal Deletion; D003176:Complement C3 / Q000276:immunology*; D003171:Complement Pathway, Classical; D018390:Gene Targeting; D007074:Immunoglobulin G / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009895:Opsonin Proteins / Q000276:immunology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D011828:Radiation Chimera; D011951:Receptors, Complement / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017463:Receptors, Complement 3b; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003176:Complement C3; C081470:Cr1l protein, mouse; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D012333:RNA, Messenger; D011951:Receptors, Complement; D017463:Receptors, Complement 3b