Interleukin-4 (IL-4)/b cell stimulatory factor-1 is a T cell derived lymphokine with potent effects on a wide variety of hempatopoietic and on some non-hematopoietic cells. It costimulates B cell DNA synthesis, acting and anti-immunoglobulin antibody to cause B cell division; it upregulates expression of class II MHC molecules and of FceRII (CD23 molecules) on resting B cells. Together with lipopolysaccharide, it strikingly enhance the production of IgG1 and of IgE and causes B cells to express Thy-1 on their membranes. The effect of IL-4 in regulating IgG1 and IgE synthesis and Thy-1 expression is also observed in cells stimulated in cogenate interactions with T cells that produce IL- 4. Moreover, anti-IL-4 treatment of mice innoculated with live Nippostrongylus brasiliensis larvae causes a virtual complete inhibition of the induction of polyclonal IgE responses. Anti-IL- 4 also inhibits IgE responses in other models of primary and secondary IgE responses. These results indicates that IL-4 is an essential factor in the in vitro regulation of IgE production. Although T cells are normally thought of as the principal if not the sole source of IL-3, IL-4 and IL-5, we have now shown that non- transformed factor-dependent mast cell lines stimulated with calcium ionophores secrete IL-3 and IL-4 and express substantial amounts of mRNA for IL-3, IL-4, and IL-5. Mast cell lines release IL-3 and express mRNA for IL-3, IL-4, and IL-5 when their Fc epsilon receptors are cross-linked. These results suggest that mast cells may participate in allergic inflammation not only through the release of vasoactive amines but also through the production of factors that regulate the growth of mast cells and eosinophils and that cause switching to the production of IgE. Efforts to characterize the IL-4 receptor and to clone the IL-4 receptor gene are in progress. In addition, a cell line has been obtained, CT.4S, that provides a specific and sensitive bioassay for IL-4, IL-3 has also been expressed in the baculovirus system, providing a source for very substantial amounts of the recombinant product.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000493-03
Application #
3818267
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Dewas, Cedric; Chen, Xi; Honda, Tetsuya et al. (2015) TSLP expression: analysis with a ZsGreen TSLP reporter mouse. J Immunol 194:1372-80
Paul, William E (2014) Endless fascination. Annu Rev Immunol 32:1-24
Ben-Sasson, S Z; Wang, K; Cohen, J et al. (2013) IL-1? strikingly enhances antigen-driven CD4 and CD8 T-cell responses. Cold Spring Harb Symp Quant Biol 78:117-24
Paul, William E; Milner, Joshua D; Grossman, Zvi (2013) Pathogen-sensing, regulatory T cells, and responsiveness-tuning collectively regulate foreign- and self-antigen mediated T-cell responses. Cold Spring Harb Symp Quant Biol 78:265-76
van Panhuys, Nicholas; Prout, Melanie; Forbes, Elizabeth et al. (2011) Basophils are the major producers of IL-4 during primary helminth infection. J Immunol 186:2719-28
Guo, Liying; Wei, Gang; Zhu, Jinfang et al. (2009) IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A 106:13463-8
Zhu, Jinfang; Davidson, Todd S; Wei, Gang et al. (2009) Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103+ inducible regulatory T cells. J Exp Med 206:329-41
Ben-Sasson, Shlomo Z; Hu-Li, Jane; Quiel, Juan et al. (2009) IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A 106:7119-24
Milner, Joshua D; Brenchley, Jason M; Laurence, Arian et al. (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773-6
Min, Booki; Paul, William E (2008) Basophils and type 2 immunity. Curr Opin Hematol 15:59-63

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