Induction of a Th1 response from Th2-polarized T cells by activated dendritic cells: Dependence on TCR:Peptide-MHC interaction, ICAM-1, IL-12, and IFN-γ

Suresh Radhakrishnan, Karla R. Wiehagen, Vesna Pulko, Virginia P. Van Keulen, William A. Faubion, Keith L. Knutson, Larry R. Pease

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Dendritic cells (DC) are important regulators of T cell immunity. The degree of stimulation, the pattern of costimulatory molecules expressed, and the cytokines secreted by DC dictate the nature of the effector and memory cells generated, particularly with respect to their Th1 or Th2 phenotypes. In this study, we demonstrate that the addition of activated DC to spleen cultures containing established Th2-polarized CD4+ T cells was sufficient to suppress Th2 and induce Th1 cytokines in a recall response, a phenomenon referred to as phenotype reversal. The ability of activated DC to induce phenotype reversal displayed exquisite Ag specificity. The DC activator B7-DC cross-linking Ab (XAb) was >10,000-fold more efficient at inducing phenotype reversal than the TLR agonists CpG-oligodeoxynucleotide and Gardiquimod. Characterization of the mechanisms governing phenotype reversal revealed the requirement for cognate interaction between the TCR:peptide-MHC complex, the expression of the costimulation/adhesion molecule ICAM-1, and secretion of IL-12 and IFN-γ by the activated DC. The requirement for the costimulation/adhesion molecule SLAM (signaling lymphocytic activation molecule) was found to be quantitative. Thus, activation of DC, particularly by crosslinking B7-DC, can modulate well-established Th2 T cell responses in an Ag-specific manner. Because the regulation of mouse and human DC by B7-DC XAb overlaps in several significant ways, immune modulation with B7-DC XAb is a potential strategy for treating Th2-mediated diseases.

Original languageEnglish (US)
Pages (from-to)3583-3592
Number of pages10
JournalJournal of Immunology
Volume178
Issue number6
StatePublished - Mar 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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