EXPRESSION OF IL-5 IN THYMOCYTES T-CELLS LEADS TO THE DEVELOPMENT OF A MASSIVE EOSINOPHILIA, EXTRAMEDULLARY EOSINOPHILOPOIESIS, AND UNIQUE HISTOPATHOLOGIES

Transgenic mice were generated using regulatory elements from the CD3 delta gene to drive T cell expression of IL-5. Expression of this cyto kine resulted in white blood cell counts that expand virtually unabate d (similar to 400,000 cells/mm(3)). This expansion is characterized by a profound eosinophilia (>60%) and commensurate increases in the abso lute numbers of all other white blood cell types. In particular, circu lating B220(+) B lymphocyte populations increased >30-fold over wild-t ype (+/+) levels. Cell differentials and expression studies using a ma rker for eosinophil precursor cells (major basic protein gene expressi on) suggest that the peripheral eosinophilia is induced primarily thro ugh the establishment of extramedullary sites of eosinophilopoiesis. T hese mice display a massive peritoneal cavity cell exudate (1-2 x 10(8 ) cells) dominated by eosinophils (similar to 50%) and the infiltratio n of eosinophils in nearly all organ systems. Sudden unexplained death occurs in 70% of all transgenic animals by 12 mo of age. Surviving tr ansgenic animals display severe inflammatory pathologies that include ulcerating skin lesions as well as lower bowel inflammation. These pat hologies parallel clinical observations of patients with a profound eo sinophilia and imply that IL-5 effector functions during some inflamma tory responses may be contingent upon peripheral lymphohemopoietic exp ression.