Overlapping roles for granulocyte-macrophage colony-stimulating factor andinterleukin-3 in eosinophil homeostasis and contact hypersensitivity

Studies of mice rendered deficient in granulocyte-macrophage colony-stimula ting factor (GM-CSF) or interleukin-3 (IL-3) have established unique roles for these cytokines in pulmonary homeostasis, resistance to infection, and antigen-specific T- and B-cell responses, In addition to these distinctive properties, however, GM-CSF and IL-3 also stimulate the development and act ivation of hematopoietic cells in many similar ways, raising the possibilit y that each factor might partially compensate for the other's absence in si ngly deficient mice. To test whether endogenous GM-CSF and IL-3 mediate red undant functions in vivo, we generated mice lacking both cytokines through sequential gene targeting experiments in embryonic stem (ES) cells. Surpris ingly, doubly deficient animals, but not single knockouts, showed increased numbers of circulating eosinophils, Doubly deficient mice, moreover, devel oped weaker contact hypersensitivity reactions to haptens applied epicutane ously then mice deficient in either factor alone. Together, these findings delineate overlapping roles for GM-CSF and IL-3 in hematopoiesis and immuni ty. (C) 2001 by The American Society of Hematology.