Treg cells mediate recovery from EAE by controlling effector T cell proliferation and motility in the CNS

Michail Koutrolos, Kerstin Berer, Naoto Kawakami, Hartmut Wekerle, Gurumoorthy Krishnamoorthy

Regulatory T cells are crucial in controlling various functions of effector T cells during experimental autoimmune encephalomyelitis. While regulatory T cells are reported to exert their immunomodulatory effects in the peripheral immune organs, their role within the central nervous system during experimental autoimmune encephalomyelitis is unclear. Here, by combining a selectively timed regulatory T cells depletion with 2-photon microscopy, we report that regulatory T cells exercise their dynamic control over effector T cells in the central nervous system. Acute depletion of regulatory T cells exacerbated experimental autoimmune encephalomyelitis severity which was accompanied by increased pro-inflammatory cytokine production and proliferation of effector T cells. Intravital microscopy revealed that, in the absence of regulatory T cells, the velocity of effector T cells was decreased with simultaneous increase in the proportion of stationary phase cells in the CNS. Based on these data, we conclude that regulatory T cells mediate recovery from experimental autoimmune encephalomyelitis by controlling effector T cells cytokine production, proliferation and motility in the CNS.