Format

Send to

Choose Destination
J Immunol. 2012 Aug 15;189(4):1850-7. doi: 10.4049/jimmunol.1201057. Epub 2012 Jul 18.

A critical role for Rictor in T lymphopoiesis.

Author information

1
Division of Immunotherapy, Department of Surgery, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.

Abstract

Apart from a critical role for Notch and pre-TCR, the signaling pathway required for T lymphopoiesis is largely unknown. Given the potential link between Notch and mammalian target of rapamycin (mTOR) signaling in cancer cells, we used mice with conditional deletion of either Raptor or Rictor genes to determine potential contribution of the mTOR complex I and II in T lymphopoiesis. Our data demonstrated that targeted mutation of Rictor in the thymocytes drastically reduced the thymic cellularity, primarily by reducing proliferation of the immature thymocytes. Rictor deficiency caused a partial block of thymocyte development at the double-negative 3 stage. The effect of Rictor deficiency is selective for the T cell lineage, as the development of B cells, erythrocytes, and myeloid cells is largely unaffected. Analysis of bone marrow chimera generated from a mixture of wild-type and Rictor-deficient hematopoietic stem cells demonstrated that the function of Rictor is cell intrinsic. These data revealed a critical function of mTOR complex 2 in T lymphopoiesis.

PMID:
22815285
PMCID:
PMC3412163
DOI:
10.4049/jimmunol.1201057
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center