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The Journal of Immunology, 2005, 174: 2242-2249.
Copyright © 2005 by The American Association of Immunologists

IL-2 and Autocrine IL-4 Drive the In Vivo Development of Antigen-Specific Th2 T Cells Elicited by Nematode Parasites1,2

Zhugong Liu3,*, Qian Liu3,*, Hossein Hamed3,*, Robert M. Anthony3,*, Anthony Foster*, Fred D. Finkelman{dagger}, Joseph F. Urban, Jr{ddagger} and William C. Gause4,*

* Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; {dagger} University of Cincinnati College of Medicine and the Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45267; and {ddagger} Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705

The intestinal nematode parasite, Nippostrongylus brasiliensis, triggers potent type 2 immunity. Using OVA peptide as a model Ag, we have examined the adjuvant effects of this parasite on the in vivo development of Ag-specific Th2 cells from naive DO11.10 T cells. Our findings show that Th2 cells can develop from transferred naive OVA-specific DO11.10 T cells in recipient IL-4–/– mice inoculated with N. brasiliensis plus OVA. However, autocrine IL-4 is required for in situ Th2 cell differentiation since transferred IL-4R{alpha}-deficient DO11.10 T cells showed greatly reduced Th2 cell development in inoculated IL-4–/– recipient mice. Surprisingly, we also found that IL-2 blockade promoted B7-dependent T cell cycling, but inhibited the development of OVA-specific Th2 cells. Furthermore, the effects of IL-2 occurred independently of CD25+ T regulatory cells. These studies establish a previously unrecognized requirement for autocrine IL-4 and IL-2 in Th2 responses elicited by nematode parasites.




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