Abstract

Two groups of experiments are planned. These problems are interconnected as both concern the murine IgE molecule. The first goal of this proposal is to continue studies of the production of anti-dinitrophenyl (DNP) IgE antibody and the influence of interleukins, especially IL-4, on the switch from IgM production to anti-DNP IgE production. Most of the previous work, published by several authors, investigated the switch from """"""""normal"""""""" polyclonal immunoglobulins of the IgM or IgG classes to polyclonal """"""""normal"""""""" IgE. The word """"""""normal"""""""" underlines that fact that the specificity of the immunoglobulins, the antigen with which they react, is unknown. Two T helper cell clones (L3T4) will be used. These clones are specific for keyhole limpet hemocyanin (KLH) and both were already investigated using B cells primed for anti-DNP antibody production. The production of anti-DNP IgM and IgG were both investigated, but not the production of anti-DNP IgE. These clones will be used together with B cells from mice syngeneic to the T cell clones. The influence of recombinant interleukins rIL-4 and rIL-2, and the influence of monoclonal anti-IL-4 and anti-IL-2 on anti-DNP IgE production will be investigated. The second goal is to study the in vitro suppression of IgE antibody specific for the DNP (dinitrophenyl) hapten. Using adoptive transfer, the applicant has demonstrated that in the SJL strain of mice, suppression of IgE antibody against DNP can be obtained. Mice primed with DNP-protein and given T cells from other mice that have been hyperprimed with an unrelated carrier protein suppress anti-DNP IgE production if this second carrier is injected. Dr. Ovary proposes to study this suppression in vitro and then instead of using hyperprimed spleen cells (plus antigen) study the possible suppressive affects in this system of different lymphokines. If successful, he proposes to use the system described above (first goal) to examine suppression of antigen specific IgE when well-defined cloned T cells are used as helper cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI003075-32
Application #
3124123
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1974-12-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
32
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012

  Publications

Maeda-Yoshimoto, K; Hirano, T; Miyajima, H et al. (1994) Suppression of IgE production in unseparated spleen cell cultures. Cell Immunol 153:277-86
Takahama, H; Ovary, Z; Furusawa, S (1994) Murine IgG1 and IgE memory B cells. Cell Immunol 157:369-80
Ueda, A; Chandswang, N; Ovary, Z (1990) The action of interleukin-4 on antigen-specific IgG1 and IgE production by interaction of in vivo primed B cells and carrier-specific cloned Th2 cells. Cell Immunol 128:31-40
Hirano, T; Yamakawa, N; Miyajima, H et al. (1989) An improved method for the detection of IgE antibody of defined specificity by ELISA using rat monoclonal anti-IgE antibody. J Immunol Methods 119:145-50
Ovary, Z (1989) The history of immediate hypersensitivity. Hosp Pract (Off Ed) 24:169-73, 177-9
Watanabe, N; Katakura, K; Kobayashi, A et al. (1988) Protective immunity and eosinophilia in IgE-deficient SJA/9 mice infected with Nippostrongylus brasiliensis and Trichinella spiralis. Proc Natl Acad Sci U S A 85:4460-2
Furusawa, S; Ovary, Z (1988) Heteroclitic antibodies: differences in fine specificities between monoclonal antibodies directed against dinitrophenyl and trinitrophenyl haptens. Int Arch Allergy Appl Immunol 85:238-43
Hirano, T; Miyajima, H; Kitagawa, H et al. (1988) Studies on murine IgE with monoclonal antibodies. I. Characterization of rat monoclonal anti-IgE antibodies and the use of these antibodies for determinations of serum IgE levels and for anaphylactic reactions. Int Arch Allergy Appl Immunol 85:47-54
Watanabe, N; Kobayashi, A; Miyajima, H et al. (1987) Detection of IgE antibody-forming cells by passive cutaneous anaphylaxis using cell extract from lymphoid organs. J Immunol Methods 96:41-5
Azuma, M; Hirano, T; Miyajima, H et al. (1987) Regulation of murine IgE production in SJA/9 and nude mice. Potentiation of IgE production by recombinant interleukin 4. J Immunol 139:2538-44

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