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Science 30 January 2004:
Vol. 303. no. 5658, pp. 685 - 689
DOI: 10.1126/science.1092138
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Reports

PEST Domain-Enriched Tyrosine Phosphatase (PEP) Regulation of Effector/Memory T Cells

Kiminori Hasegawa,1 Flavius Martin,1 Guangming Huang,1 Dan Tumas,2 Lauri Diehl,1,2 Andrew C. Chan1*

Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain–enriched tyrosine phosphatase (PEP) in regulating T cell antigen–receptor function during thymocyte development and peripheral T cell differentiation. Although normal naïve T cell functions were retained in pep-deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function.

1 Department of Immunology, Genentech, Inc., One DNA Way, South San Francisco, CA 94080, USA
2 Department of Pathology, Genentech, Inc., One DNA Way, South San Francisco, CA 94080, USA

* To whom correspondence should be addressed: acc{at}gene.com

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