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(H)1-dominated immune responses and co-express T-bet together with Foxp3. This allows for expression of CXCR3 and efficient homing to sites of T(H)1 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.