CD4 + CD25 + FoxP3 + regulatory T cells suppress cytotoxicity of CD8 + effector T cells: Implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level

Background: cd4 +cd25 +forkhead box p3 (foxp3) +regulatory t cells (t reg cells) are known to suppress adaptive immune responses,key control tolerance and autoimmunity.methods: we challenged the role of cd4 +t reg cells in suppressing established cd8 +t effector cell responses by using the ot-i/ii system in vitro and an ot-i-mediated,oligodendrocyte directed ex vivo model (odc-ova model).results: cd4 +t reg cells dampened cytotoxicity of an ongoing cd8 +t effector cell attack in vitro and within intact central nervous system tissue ex vivo. however,their suppressive effect was limited by the strength of the antigen signal delivered to the cd8 +t effector cells and the ratio of regulatory to effector t cells. cd8 +t effector cell suppression required t cell receptor-mediated activation together with costimulation of cd4 +t reg cells,but following activation,suppression did not require restimulation and was antigen non-specific.conclusions: our results suggest that cd4 +t reg cells are capable of suppressing cd8 +t effector cell responses at the parenchymal site,that is,limiting parenchymal damage in autoimmune central nervous system inflammation. © 2012 göbel et al; licensee biomed central ltd.