Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs

INTRODUCTION: Most T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown. METHODS: In this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4(+) T cells in vivo, in the absence of intentional antigenic stimulation. RESULTS: Our data show that both T cell subsets polarize into type 1 Tconvs or Tregs, characterized by cell activation, cytokine production, response to IFN-γ and CXCR3-dependent migration to inflammatory sites. Transfer experiments suggest that CD27 engagement triggers Treg activation in a cell autonomous fashion. CONCLUSION: We conclude that CD27 may regulate the development of Th1 immunity in peripheral tissues as well as the subsequent switch of the effector response into long-term memory.