Human CD4 super(+) T Cells Express TLR5 and Its Ligand Flagellin Enhances the Suppressive Capacity and Expression of FOXP3 in CD4 super(+)CD25 super(+) T Regulatory Cells

• Published in: Journal of Immunology 2005-12, Vol.175 (12), p.8051-8059
• Main Authors: Crellin, Natasha K, Garcia, Rosa V, Hadisfar, Omeed, Allan, Sarah E, Steiner, Theodore S, Levings, Megan K
• Format: Article
• Language: English
• ISSN: 0022-1767; 1365-2567

Germline encoded pattern recognition receptors, such as TLRs, provide a critical link between the innate and adaptive immune systems. There is also evidence to suggest that pathogen-associated molecular patterns may have the capacity to modulate immune responses via direct effects on CD4 super(+) T cells. Given the key role of both CD4 super(+)CD25 super(+) T regulatory (Treg) cells and the TLR5 ligand flagellin in regulating mucosal immune responses, we investigated whether TLR5 may directly influence T cell function. We found that both human CD4 super(+)CD25 super(+) Treg and CD4 super(+)CD25 super(-) T cells express TLR5 at levels comparable to those on monocytes and dendritic cells. Costimulation of effector T cells with anti-CD3 and flagellin resulted in enhanced proliferation and production of IL-2, at levels equivalent to those achieved by costimulation with CD28. In contrast, costimulation with flagellin did not break the hyporesponsiveness of CD4 super(+)CD25 super(+) Treg cells, but rather, potently increased their suppressive capacity and enhanced expression of FOXP3. These observations suggest that, in addition to their APC-mediated indirect effects, TLR ligands have the capacity to directly regulate T cell responses and modulate the suppressive activity of Treg cells.