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The role of the PI3K-AKT kinase pathway in T-cell development beyond the β checkpoint by Ling Xue; Leslie Chiang; Chulho Kang; Astar Winoto is a Immunology and Microbiology article available to read on EtoBox.

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## Abstract The PI3K‐AKT pathway can mediate diverse biological responses and is crucial for optimal immune responses and lymphocyte development. Deletion of PI3K subunits or AKT leads to blockage of T‐cell development at the TCR‐β checkpoint. Studies with over‐expression of constitutively activated AKT have implicated this pathway in anti‐apoptosis of developing thymocytes and in development of regulatory T cells. However, the role of endogenous PI3K‐AKT in T‐cell development beyond the TCR‐β checkpoint remains unclear. Here, we inhibited the endogenous PI3K‐AKT pathway in thymocytes after double negative stages by expressing the negative regulator, PTEN. These mice exhibit normal early T‐cell development, but the transition from intermediate single positive to double positive (DP) thymocytes is inhibited, leading to a significantly decreased number of DP, single positive thymocytes and peripheral T cells. Proliferation of peripheral T cells is reduced but apoptosis of DP cells and subsequent T‐cell maturation, including regulatory T cells, are normal. AKT phosphorylation can be readily observed in most WT T‐cell compartments but not DP thymocytes in response to TCR activation. Th

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Author

Ling Xue; Leslie Chiang; Chulho Kang; Astar Winoto

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Ltd.; Wiley (ISSN 0014-2980)

Published

2008

Language

EN

Field

Immunology and Microbiology (Life Sciences)