Premium
PS80 interferes with the antiallergic effect of Cry‐consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, at very low concentration through modulation of Th1/Th2 balance
Author(s) -
Kozutsumi Daisuke,
Tsunematsu Masako,
Yamaji Taketo,
Murakami Rika,
Yokoyama Minehiko,
Kino Kohsuke
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02390.x
Subject(s) - peptide , chemistry , antigen , splenocyte , sensitization , immunology , antibody , biology , biochemistry
Summary Polysorbate 80 (PS80 or Tween‐80) is often used as an additive to promote the rapid solubilization of pharmaceuticals in aqueous solutions. We investigated whether coinjection of a minimal amount of PS80 had a modulatory effect on the immunotherapeutic effects of Cry (Cryptomeria)‐consensus peptide, a novel peptide developed for the therapeutic management of Japanese cedar pollinosis, using a Cry j 1‐sensitized mouse model with experimental allergic rhinitis. Subcutaneous challenge with Cry‐consensus peptide plus 50 µg/ml of PS80 did not affect the antigen‐specific proliferation of splenocytes, but decreased the potency of Cry‐consensus peptide to inhibit antigen‐specific interleukin (IL)‐5 production by the cells significantly in comparison with challenge with Cry‐consensus peptide alone. However, there was no significant difference between the effect of Cry‐consensus peptide administration on interferon (IFN)‐γ production in the presence and absence of PS80, indicating that PS80 interfered with the T helper 1 (Th1)‐dominant T helper balance induced by Cry‐consensus peptide challenge. Moreover, the increase in the level of antigen‐specific immunoglobulin G2a (IgG2a) induced by Cry‐consensus peptide challenge was inhibited slightly but unambiguously by PS80 coinjection. These in vitro experiments indicated that PS80 induces Th2‐type differentiation of T helper cells through preferential inhibition of IFN‐γ expression relative to IL‐5 expression in splenocytes in a concentration‐dependent manner. In naïve mice, sensitization by Cry‐consensus peptide with PS80 induced antigen‐specific IL‐5 production more potently than sensitization by Cry‐consensus peptide alone, and when PS80 was added to bone marrow‐derived dendritic cells, the endocytosis of fluorescence‐labelled Cry‐consensus peptide was dramatically inhibited in a concentration‐dependent manner. Therefore, we conclude that PS80 has an immunomodulatory effect on the antigen‐specific response resulting in a shift towards Th2 predominance with respect to the antigen recognition stage. Taken together, our findings suggest that PS80 might decrease the efficacy of Cry‐consensus peptide through modulation of the efficiency of antigen endocytosis and/or of the direction of successive T helper cell differentiation.