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Updated: Aug 4, 2026
Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
Published on: April 3, 2011
Expression of the p56(Lck) Y505F mutation in CD45-deficient mice rescues thymocyte development
J R Seavitt1, L S White, K M Murphy
1Center for Immunology, Department of Pathology and Howard Hughes Medical Institute, Washington University, St. Louis, Missouri 63110, USA.
Abstract:
Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhibit a block in thymocyte development. To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient mice that express transgenes for the Lck Y505F mutation and the DO11.10 T-cell antigen receptor (TCR). CD4 single-positive T cells developed and accumulated in the periphery. Treatment with antigen resulted in thymocyte apoptosis and the loss of transgenic-TCR-bearing cells. Peripheral CD45-deficient T cells from the mice expressing both transgenes responded to antigen by increasing CD69 expression, interleukin-2 production, and proliferation. These results indicate that thymocyte development requires the dephosphorylation of the inhibitory site in Lck by CD45.
Insights
The transmembrane protein tyrosine phosphatase CD45 is crucial for thymocyte development. CD45 dephosphorylates p56(lck) (Lck), enabling T-cell maturation and preventing thymocyte apoptosis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Transmembrane protein tyrosine phosphatase CD45 plays a role in lymphocyte development.
- CD45 deficiency in mice leads to a developmental block in thymocytes.
- The inhibitory phosphorylation site (Y505) in p56(lck) (Lck) is a key regulator of T-cell receptor signaling.
Purpose of the Study:
- To investigate the role of CD45 in dephosphorylating the inhibitory site of Lck.
- To determine if CD45-mediated dephosphorylation of Lck is essential for thymocyte development.
Main Methods:
- Generated CD45-deficient mice expressing transgenes for the Lck Y505F mutation and the DO11.10 T-cell receptor (TCR).
- Analyzed thymocyte development, peripheral T-cell accumulation, and T-cell responses to antigen stimulation.
Main Results:
- CD4 single-positive T cells developed and accumulated in the periphery in CD45-deficient mice with the Lck Y505F mutation.
- Antigen treatment induced thymocyte apoptosis and loss of transgenic TCR-bearing cells.
- Peripheral T cells exhibited increased CD69 expression, IL-2 production, and proliferation upon antigen stimulation.
Conclusions:
- Thymocyte development necessitates the dephosphorylation of the inhibitory site in Lck by CD45.
- CD45-mediated dephosphorylation of Lck is critical for proper T-cell maturation and preventing aberrant thymocyte proliferation.
