Oral administration of a dominant T-cell determinant peptide inhibits allergen-specific TH1 and TH2 cell responses in Cry j 2-primed mice.
BACKGROUND
Oral immunotherapy with a peptide for allergic immune responses is theoretically a promising therapy but has not been established yet.


OBJECTIVE
To evaluate immune suppressive efficacy of oral administration of an immunodominant peptide, we investigated changes in T-cell proliferation, TH1 - and TH2 -cytokine production, and TH1 - and TH2 -mediated antibody production in mice after oral administration of a peptide.


METHODS
Peptide p246-259, containing a dominant T-cell determinant of Cry j 2, which is the major allergen in Japanese cedar pollen, was used in this study. Groups of mice received p246-259 or PBS alone before or after they were primed intranasally with Cry j 2 and cholera toxin. In another experiment mice were primed intraperitoneally with Cry j 2 and alum. Proliferative response and cytokine production by nasal-associated lymph node cells against Cry j 2 were investigated. Amounts of systemic anti-Cry j 2 IgE and IgG antibodies were also measured.


RESULTS
Oral administration of the peptide to mice before, or even after, the sensitization induced oral tolerance in T-cell responses against the allergen; the tolerance was associated with decreased production of TH1 (IFN-gamma and IL-2) and TH2 (IL-4) cytokines. Allergen-specific TH1 -mediated (IgG2a and IgG2b) and TH2 -mediated (IgG1 and IgE) antibody responses were also inhibited.


CONCLUSIONS
Oral administration of a dominant T-cell determinant peptide induces immunologic tolerance in both TH1 and TH2 cell responses against the whole protein allergen. Our study is the first, to our knowledge, to demonstrate the potential for peptide-based oral immunotherapy in order to treat allergic immune responses.
Hirahara
K
K
Sankyo Co, Ltd, Tokyo.
Saito
S
S
Serizawa
N
N
Sasaki
R
R
Sakaguchi
M
M
Inouye
S
S
Taniguchi
Y
Y
Kaminogawa
S
S
Shiraishi
A
A
D000281:Administration, Intranasal; D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D016056:Immunodominant Epitopes / Q000008:administration & dosage*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D010940:Plant Proteins / Q000008:administration & dosage*; D011058:Pollen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014197:Trees
D000485:Allergens; C065291:Cry j II protein, Cryptomeria japonica; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D010940:Plant Proteins; D007073:Immunoglobulin E; D002772:Cholera Toxin