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 Blood, 15 December 2007, Vol. 110, No. 13, pp. 4367-4369.
Prepublished online as a Blood First Edition Paper on September 18, 2007; DOI 10.1182/blood-2007-06-098244.

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IMMUNOBIOLOGY

Brief Report

Constitutively active STAT6 predisposes toward a lymphoproliferative disorder

Mark H. Kaplan1, Sarita Sehra1, Hua-Chen Chang1, John T. O'Malley1, Anubhav N. Mathur1, and Heather A. Bruns2

1 Departments of Pediatrics and Microbiology and Immunology, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN; and 2 Department of Biology, Ball State University, Muncie, IN

Signal transducer and activator of transcription 6 (STAT6) is critical for IL-4 and IL-13 responses, and necessary for the normal development of Th2 cells. We previously generated mice that express a constitutively active STAT6 (STAT6VT) under control of the CD2 locus control region, which directs expression to the T-cell compartment. We now describe that a small proportion of these mice (~5%) develop a spontaneous lymphoproliferative disease (LPD) that results in dramatic splenomegaly. The cell populations observed in the LPD spleens can be divided into 2 categories, those that are composed of mixed lineage cells and those that are predominantly T cells with a phenotype similar to that in autoimmune lymphoproliferative syndrome (ALPS) patients. These data suggest that while active STAT6 is not a transforming factor, expression in T cells predisposes toward the development of lymphoproliferative disorders.


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