Control of the specificity of T cell-mediated anti-idiotype immunity by natural regulatory T cells

Max Warncke, Maike Buchner, Gudrun Thaller, Anna Dodero, Alla Bulashevska, Dietmar Pfeifer, Jens Timmer, Hendrik Veelken

Research output: Contribution to journalArticle

Abstract

The idiotypes of B cell lymphomas represent tumor-specific antigens. T cell responses induced by idiotype vaccination in vivo are directed predominantly against CDR peptides, whereas in vitro T cells also recognize framework-derived epitopes. To investigate the mechanisms regulating the specificity of idiotype-specific T cells, BALB/c or B10.D2 mice were immunized with mature dendritic cells loaded with H-2Kd-restricted peptides from influenza hemagglutinin, or from shared (J region) or unique (CDR3) structures of the A20 lymphoma idiotype. Antigen-specific T cells were induced in vivo by the CDR3 and influenza epitopes, but not by the J peptide. Gene expression profiling of splenic regulatory T cells revealed vaccination-induced Treg activation and proliferation. Treg activity involved J epitope-dependent IL-10 secretion and functional suppression of peptide-specific effector T cells. Vaccination-induced in vivo proliferation of transgenic hemagglutinin-specific T cells was suppressed by co-immunization with the J peptide and was restored in CD25-depleted animals. In conclusion, Treg induced by a shared idiotype epitope can systemically suppress T cell responses against idiotype-derived and immunodominant foreign epitopes in vivo. The results imply that tumor vaccines should avoid epitopes expressed by normal cells in the draining lymph node to achieve optimal anti-tumor efficacy.

Original languageEnglish
Pages (from-to)49-60
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume60
Issue number1
DOIs
Publication statusPublished - Jan 2011

Keywords

  • FoxP3
  • Idiotype
  • Lymphoma
  • Regulatory T cell

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

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