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Blood, 15 February 2001, Vol. 97, No. 4, pp. 922-928
HEMATOPOIESIS
Overlapping roles for granulocyte-macrophage colony-stimulating
factor and interleukin-3 in eosinophil homeostasis and contact
hypersensitivity
Silke Gillessen,
Nicolas Mach,
Clayton Small,
Martin Mihm, and
Glenn Dranoff
From the Department of Adult Oncology, Dana-Farber
Cancer Institute and Department of Medicine, Harvard Medical School,
Boston, MA; Division of Oncology, Department of Internal Medicine,
Geneva University Hospital, Geneva, Switzerland; and Department of
Pathology, Massachusetts General Hospital, Boston, MA.
Studies of mice rendered deficient in granulocyte-macrophage
colony-stimulating 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 activation of hematopoietic cells in
many similar ways, raising the possibility that each factor might
partially compensate for the other's absence in singly deficient mice.
To test whether endogenous GM-CSF and IL-3 mediate redundant functions
in vivo, we generated mice lacking both cytokines through sequential
gene targeting experiments in embryonic stem (ES) cells. Surprisingly,
doubly deficient animals, but not single knockouts, showed increased
numbers of circulating eosinophils. Doubly deficient mice, moreover,
developed weaker contact hypersensitivity reactions to haptens applied
epicutaneously than mice deficient in either factor alone. Together,
these findings delineate overlapping roles for GM-CSF and IL-3 in
hematopoiesis and immunity.

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