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Sensitive1
*
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-.
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