Alpha-galactosylceramide-driven immunotherapy for allergy.
We report here that the delivery of both alpha-galactosylceramide (alphaGalCer), a representative ligand for invariant natural killer T (iNKT) cells, and an antigenic polypeptide to marginal zone B cells induces the differentiation of regulatory cells in vivo, and suppresses the secondary antibody responses in mice. Splenic CD21+ CD23- B cells of mice treated with alphaGalCer-liposomes produce IL-10 when co-cultured with iNKT cells, whereas the cells treated with aqueous alphaGalCer fail to do so. Adoptive transfer of the B cells into syngenic mice leads to the expansion of splenic CD11c(low) CD45RB(high) cells, which convert naive CD4+ T cells from RAG2-deficient DO11.10 mice to CD4+ CD25(high) Foxp3+ T cells in the presence of OVA323-339 peptide. Administration of alphaGalCer-OVA-liposomes into OVA-primed mice causes the development of CD4+ CD25(high) Foxp3+ T cells that produce both IL-10 and IFN-gamma, and induced the antigen-specific suppression of the secondary antibody responses when boosted with OVA alone. These results indicate that antigen-containing alphaGalCer-liposomes can facilitate the development of tolerogenic antigen-presenting cells and inducible regulatory T cells that are involved in the suppression of immune responses to antigens.
Laboratory for Vaccine Design, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehiro, Tsurumi, Yokohama, Kanagawa, Japan 230-0045. ishiiyas@rcai.riken.jp
Yasuyuki
Y
Ishii
Risa
R
Nozawa
Yukiko
Y
Takamoto-Matsui
Annabelle
A
Teng
Haruka
H
Katagiri-Matsumura
Hiroshi
H
Nishikawa
Hiroyuki
H
Fujita
Yuki
Y
Tamura
D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018899:CpG Islands / Q000276:immunology; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D018926:Anti-Allergic Agents; D005699:Galactosylceramides; D008081:Liposomes; C493154:alpha-galactosylceramide