Responses to the soluble flagellar protein FliC are Th2, while those to FliC on Salmonella are Th1

Eur J Immunol. 2004 Nov;34(11):2986-95. doi: 10.1002/eji.200425403.

Abstract

Features of the Th1 or Th2 phenotype start to develop during CD4 T cell priming. This study of the response to the bacterial flagellar protein FliC shows that either Th1 or Th2 responses can be induced in mice depending upon how FliC is presented. This is shown by assessing the cytokine mRNA and class of FliC-specific plasma cells induced in situ. Soluble recombinant (r)FliC and polymerized FliC are strongly Th2 polarizing, inducing IL-4, NIP45 and c-Maf mRNA as well as epsilon and gamma1 switch transcripts and switching to IgG1. CD28-requirement for this switching shows its T cell dependence. rFliC was unable to induce markers of Th1 activity including IL-12, T-bet and IFN-gamma. Conversely, when FliC is presented in its native context surface-bound on live, flagellated Salmonella, switching is predominantly to IgG2a (IgG2c in C57BL/6 mice), reflecting Th1 activity. The development of divergent FliC-specific polarization to either Th1 or Th2 indicates that the context in which this antigen is encountered rather than its intrinsic immunostimulatory properties determines the direction of Th polarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Bacterial / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Flagellin / immunology*
  • Flagellin / isolation & purification
  • Flagellin / pharmacology
  • Immunization
  • Immunoglobulin Class Switching
  • Immunoglobulin G / immunology
  • Lymph Nodes / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasma Cells / drug effects
  • Plasma Cells / immunology
  • RNA / chemistry
  • RNA / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmonella / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Cytokines
  • Immunoglobulin G
  • Recombinant Proteins
  • Flagellin
  • RNA