Submitted June 26, 2007
Accepted September 15, 2007
Constitutively active Stat6 predisposes towards a lymphoproliferative disorder
Mark H Kaplan*, Sarita Sehra, Hua-Chen Chang, John T O'Malley, Anubhav N Mathur, and Heather A Bruns
Departments of Pediatrics, and Microbiology and Immunology, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
Department of Biology, Ball State University, Muncie, IN, United States
* Corresponding author; email: mkaplan2{at}iupui.edu.
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 have 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 two categories, those that are comprised 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 towards the development of lymphoproliferative disorders.
