Myelin specific regulatory T cells expand from naturally occurring regulatory T cells and accumulate in the CNS during EAE (128.8)

Abstract

Abstract FoxP3 is a lineage specific marker for regulatory T cells (T-reg). We have generated FoxP3 knock-in mice by introducing a bicistronic GFP reporter into the endogenous FoxP3 locus, allowing us to faithfully track T-reg in vivo. We have also generated a MOG 35-55/IAb-tetramer. The combination of these two technologies enables us to study the in vivo behavior of myelin specific T-reg and effector T cells (T-eff) during EAE. Upon immunization with MOG 35-55, we identified a population of MOG-tetramer-reactive T-reg in the peripheral lymphoid compartment. T-reg trafficked to the CNS where they were readily detected as early as day 10 following immunization. At this stage and till the peak of the disease, an overwhelming number of T-eff also targeted the CNS. Thus, the ratio of T-reg and T-eff at the initiation of disease was 1:15. However at the onset of recovery, this ratio changed in favor of T-reg (T-reg/T-eff close to 1:1. During recovery, 50% of the CNS-derived T-reg were IL-10 producers compared to only 10% in the peripheral immune compartment. FOXP3+ T cells isolated from the CNS are effective in suppressing naive MOG-specific T cells, but fail to control CNS-derived T-eff that secrete IL-6 and TNF. Our data suggest that in order for CD4+FOXP3+ T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation