Faculty Collaboration Database

Jak3 selectively regulates Bax and Bcl-2 expression to promote T-cell development. Mol Cell Biol 2001 Jan;21(2):678-89

Date

01/03/2001

Pubmed ID

11134353

Pubmed Central ID

PMC86650

DOI

10.1128/MCB.21.2.678-689.2001

Scopus ID

2-s2.0-0035159241 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

Jak3-deficient mice display vastly reduced numbers of lymphoid cells. Thymocytes and peripheral T cells from Jak3-deficient mice have a high apoptotic index, suggesting that Jak3 provides survival signals. Here we report that Jak3 regulates T lymphopoiesis at least in part through its selective regulation of Bax and Bcl-2. Jak3-deficient thymocytes express elevated levels of Bax and reduced levels of Bcl-2 relative to those in wild-type littermates. Notably, up-regulation of Bax in Jak3-deficient T cells is physiologically relevant, as Jak3 Bax double-null mice have marked increases in thymocyte and peripheral T-cell numbers. Rescue of T lymphopoiesis by Bax loss was selective, as mice deficient in Jak3 plus p53 or in Jak3 plus Fas remained lymphopenic. However, Bax loss failed to restore proper ratios of peripheral CD4/CD8 T cells, which are abnormally high in Jak3-null mice. Transplantation into Jak3-deficient mice of Jak3-null bone marrow transduced with a Bcl-2-expressing retrovirus also improved peripheral T-cell numbers and restored the ratio of peripheral CD4/CD8 T cells to wild-type levels. The data support the concepts that Jak kinases regulate cell survival through their selective and cell context-dependent regulation of pro- and antiapoptotic Bcl-2 family proteins and that Bax and Bcl-2 play distinct roles in T-cell development.

Author List

Wen R, Wang D, McKay C, Bunting KD, Marine JC, Vanin EF, Zambetti GP, Korsmeyer SJ, Ihle JN, Cleveland JL

Author

Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
CD4-CD8 Ratio
CD8-Positive T-Lymphocytes
Cell Differentiation
Cell Survival
Flow Cytometry
Fluorescent Antibody Technique
Gene Deletion
Gene Expression Regulation
In Situ Nick-End Labeling
Janus Kinase 3
Mice
Mice, Knockout
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
T-Lymphocytes
Thymus Gland
bcl-2-Associated X Protein