Preceding Viral Infections Do Not Imprint Long-Term Changes in Regulatory T Cell Function

Regulatory T cells (T_regs) maintain peripheral self-tolerance and limit immune mediated pathology. Like effector T cells, T_regs can specialize in T_H1-dominated immune responses and co-express T-bet together with Foxp3. This allows for expression of CXCR3 and efficient homing to sites of T_H1 responses. However, whether such functional specialization is paralleled by memory generation among T_regs is unknown. In this study, we investigated the ability of polyclonal T_regs to form functional memory in response to viral infection. Using adoptive transfer models to compare infection-experienced T_regs generated upon acute Lymphocytic Choriomeningitis Virus (LCMV) WE and Vaccinia Virus (VV) infections with naive T_regs, we observed no differences in their phenotype or their in vivo maintenance. When comparing functional properties of infection-experienced and naive T_regs, we found no differences in in vitro suppressive capacity nor in their ability to limit the effector response upon homologous, systemic or local re-challenge in vivo. Our results suggest that no functional T_reg memory is generated in the context of systemic LCMV or VV infection, but we cannot rule out the possibility that the generation of T_reg memory may be possible in other contexts.