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IL-13-Mediated Worm Expulsion Is B7 Independent and IFN- Sensitive¹

Joseph Urban^*, Hui Fang^2,, Qian Liu^2,, Melinda J. Ekkens, Shen-Jue Chen, Diep Nguyen, Velia Mitro, Debra D. Donaldson, Colleen Byrd, Robert Peach^§, Suzanne C. Morris^¶, Fred D. Finkelman^¶, Lisa Schopf^* and William C. Gause^3,

^* Immunology Disease Resistance Laboratory, Livestock and Poultry Sciences Institute, U.S. Department of Agriculture, Beltsville, MD 20705; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; Genetics Institute, Cambridge, MA 02140; ^§ Immunology and Inflammation, Bristol-Myers Squibb, Princeton, NJ 08543; and ^¶ Department of Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267 and Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220

B7 costimulation is a required component of many type 2 immune responses, including allergy and protective immunity to many nematode parasites. This response includes elevations in Th2 cytokines and associated effector functions including elevations in serum IgG1 and IgE and parasite expulsion. In studies of mice infected with Trichuris muris, blocking B7 ligand interactions inhibited protective immunity, suppressed IL-4 production, and enhanced IFN- production, but unexpectedly did not inhibit production of the Th2 cytokine, IL-13. Blocking both IFN- and B7 restored protective immunity, which was IL-13 dependent, but did not restore IL-4 or associated IgE responses. Although IL-13 was required for worm expulsion in mice in which both IFN- and B7 were blocked, IL-4 could mediate expulsion in the absence of both IL-13 and IFN-. These studies demonstrate that 1) B7 costimulation is required to induce IL-4, but not IL-13 responses; 2) IL-13 is elevated in association with the IFN- response that occurs following inhibition of B7 interactions, but can only mediate IL-4-independent protection when IFN- is also inhibited; and 3) increased IL-13 production, in the absence of increased IL-4 production, is not associated with an IgE response, even in the absence of IFN-.