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Complement-dependent T-cell lymphopenia caused by thymocyte deletion of the membrane complement regulator Crry.

ABSTRACT: 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.

SUBMITTER: Miwa T

PROVIDER: S-EPMC2661856 | biostudies-other | 2009 Mar

REPOSITORIES: biostudies-other

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Complement-dependent T-cell lymphopenia caused by thymocyte deletion of the membrane complement regulator Crry.

Miwa Takashi T Zhou Lin L Kimura Yuko Y Kim David D Bhandoola Avinash A Song Wen-Chao WC

Blood 20090109 12

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 ...[more]

PMID: 19136662

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