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

• Published in: Blood Vol. 97; no. 4; pp. 922 - 928
• Main Authors: GILLESSEN, Silke, MACH, Nicolas, SMALL, Clayton, MIHM, Martin, DRANOFF, Glenn
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.02.2001
• Subjects: Animals; Biological and medical sciences; Dendritic Cells - cytology; Dermatitis, Contact - genetics; Dermatitis, Contact - pathology; Dermatitis, Contact - physiopathology; Eosinophilia - genetics; Eosinophils; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Targeting; Granulocyte-Macrophage Colony-Stimulating Factor - deficiency; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - physiology; Haptens - immunology; Hematopoiesis - genetics; Homeostasis; Immunobiology; Interleukin-3 - deficiency; Interleukin-3 - genetics; Interleukin-3 - physiology; Leukocyte Count; Membrane Proteins - metabolism; Mice; Mice, Knockout; Modulation of the immune response (stimulation, suppression); Neoplasm Transplantation; Oxazolone - toxicity; Skin - immunology; Skin - pathology; Tumor Cells, Cultured - metabolism; Animal model; Immune response; Immunomodulation; Cytokine; Rodentia; Granulocyte; Biological activity; Eosinophil; Vertebrata; Mammalia; Mouse; Polypeptide; Hematopoiesis; Interleukin 3; Animal; Granulocyte macrophage colony stimulating factor; Contact hypersensitivity
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.4.922

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. (Blood. 2001;97:922-928)