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United States Department of Agriculture

Agricultural Research Service

Title: Stat6 Regulation of in Vivo Il-4 Response

Authors
item Finkelman, Fred - DIV IMMUN OHIO
item Morris, Suzanne - DIV IMMUN OHIO
item Orekhova, Tatyana - DIV IMMUN OHIO
item Mori, Masaaki - DIV IMMUN OHIO
item Donaldson, Debra - CAMBRIDGE MA
item Reiner, Steven - U CHICAGO ILLINOIS
item Reilly, Nancy - U CHICAGO ILLINOIS
item Schopf, Lisa
item Urban, Joseph

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 7, 1999
Publication Date: March 1, 2000
Citation: Finkelman, F.D., Morris, S.C., Orekhova, T., Mori, M., Donaldson, D., Reiner, S., Reilly, N.L., Schopf, L.R., Urban Jr, J.F. 2000. Stat6 regulation of in vivo il-4 response. Journal of Immunology.164:2303-2310 (2000)

Interpretive Summary: Protective immunity to a wide variety of gastrointestinal (GI) nematode parasites is related to a type 2 immune response pattern. Infections of livestock with GI nematodes remain a major economic and general health issue for producers. There is a need to find alternatives to chemical control strategies for protecting livestock against infection. The immune system provides natural control mechanisms that are characterized by specificity and long term memory. An understanding of the basic control elements of memory responses can be useful in designing more efficient vaccines. The current study demonstrates that an intracellular Stat6 molecule regulates a central component of the type 2 immune response. It is most important in controlling the memory response to certain allergens and GI nematode products that induce an immune response. The production of agonists that stimulate Stat6 are likely to enhance the level of protective eimmunity to GI nematodes. These results will be important to government, academic and industry scientists that require basic information on the immune system to improve immunization procedures.

Technical Abstract: The in vitro development of a Th2 response from naive CD4+ cells is Stat6-dependent, however, some immunogens induce normal in vivo primary IL-4 responses in Stat6-deficient mice. The ability of an immunogen to induce a primary IL-4 response varies directly with its ability to induce a type 2 cytokine-biased response in normal mice. Immunogens that induce a strong primary IL-4 response in Stat6-deficient mice evoke a poor memory IL-4 response. These observations are consistent with the fact that Stat6-deficient CD4+ T cells make relatively normal IL-4 response when stimulated in vitro with anti-CD3 and anti-CD28, but poor IL-4 response when stimulated later with anti-CD3. Thus, Stat6 signaling enhances weak primary IL-4 responses and is required for normal development and/or survival of Th2 memory cells both in vitro and in vivo.

Last Modified: 9/21/2014
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