Disruption of Lymphocyte Function and Signaling in CD45–associated Protein–null Mice

Matsuda, Akio; Motoya, Satoshi; Kimura, Shioko; McInnis, Renee; Maizel, Abby L.; Takeda, Akiko

doi:10.1084/jem.187.11.1863

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Article| June 01 1998

Disruption of Lymphocyte Function and Signaling in CD45–associated Protein–null Mice

Akio Matsuda,

Akio Matsuda

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

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Satoshi Motoya,

Satoshi Motoya

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

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Shioko Kimura,

Shioko Kimura

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

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Renee McInnis,

Renee McInnis

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

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Abby L. Maizel,

Abby L. Maizel

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

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Akiko Takeda

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

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Author and Article Information

Akio Matsuda

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Satoshi Motoya

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Shioko Kimura

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Renee McInnis

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Abby L. Maizel

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Akiko Takeda

From the *Department of Pathology, Roger Williams Hospital-Brown University, Providence, Rhode Island 02908; and the ‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Address correspondence to Akiko Takeda, Department of Pathology, Roger Williams Hospital-Brown University, 825 Chalkstone Ave., Providence, RI 02908. Phone: 401-456-6557; Fax: 401-456-6569; E-mail: [email protected]

Satoshi Motoya's present address is First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan 060

Received: December 30 1997

Revision Received: March 04 1998

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1998

J Exp Med (1998) 187 (11): 1863–1870.

https://doi.org/10.1084/jem.187.11.1863

CD45-AP specifically associates with CD45, a protein tyrosine phosphatase essential for lymphocyte differentiation and antigen receptor–mediated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src family protein tyrosine kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP–null mice were created to examine the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes showed reduced proliferation in response to antigen receptor stimulation. Both mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were also markedly decreased in CD45-AP–null mice. Interestingly, the interaction between CD45 and Lck was significantly reduced in CD45-AP–null T cells, indicating that CD45-AP directly or indirectly mediates the interaction of CD45 with Lck. Our data indicate that CD45-AP is required for normal antigen receptor signaling and function in lymphocytes.

1998

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