Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4⁺ T Cell Response

Immunity Volume 25, Issue 4, October 2006

Speaker: 鄭元鈞                                                           Place: Room 601

Commentator: 胥直利 老師                                       Date: 2007/5/23  13:00~14:00

Abstract

Toll-like receptors recognition can activate antigen presenting cells to stimulate T cell responses.  Previous studies showed that TLR ligand interacted with dendritic cells directly affected antigen uptake.  DCs without MyD88- dependent TLR signaling failed to present antigens and failed to stimulate CD4⁺ T cells.  These studies suggested that TLR signaling has corelation with regulation of T cell activation.  In order to investigate the role of TLR in regulating DCs to stimulate T cell response, the author demonstrated the role of TLR recognition in governing CD4⁺ T cell response to Toxoplasma gondii.  Profilin, a component of STAg, is a TLR11 ligand.  Therefore, the authors immunized wild type, Tlr11T^-/-, or Myd88^-/- C57BL/6 mice with STAg and isolated the immunized CD4⁺ T cells.  They isolated splenocytes from unimmunized mice as antigen presenting cells and cocultured with immunized CD4⁺ T cells in medium containing STAg or profiling and evaluated the T cell response.  First they found that the immunodominance of profilin depended on TLR11 and MyD88 dependent signaling to activateCD4⁺ T cell response.  Second, they isolated the CD11c⁺ spleen cells as APCs and repeated above experiment.  They found that only CD11c⁺ CD8α⁺ DC can be primed by STAg or profilin and stimulate profiling-specific CD4⁺ T cells.  Third, they used CpG oligonucleotides, a TLR9 ligand, conjugated with ovalbumin to immunized wild type, Tlr9^-/-, or Myd88^-/- C57BL/6 mice mice and evaluated CD4⁺ T cell response to ovalbumin.  They found that CpG oligonucleotides onjugated with ovalbumin can induce CD4⁺ T cell response via TLR9/MyD88 dependent mechanism.  The result demonstrated that other TLR can induce the mechanism like TLR11 regulating immunodominance in CD4⁺ T cell.  The authors considered that TLRs of DCs are not only a pathogen sensor of DCs activation, but also regulates the antigen uptake and presentation of DC to stimulate immunodominant Ag-specific CD4⁺ T cell response.

Reference

1. Blander, J.M., and Medzhitov  Toll-dependent selection of microbial antigens for presentation by dendritic cells.  Nature 440, 808–812. (2006)

2. Yarovinsky, F., and Sher, A. Int. J. Parasitol. Toll-like receptor recognition of Toxoplasma gondii. (2006) 36, 255–259.