IL-2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8⁺ T cells

Demyelination, one of the major pathological changes of white matter injury, is closely related to T-cell-mediated immune responses. Thus, we investigate the role of an IL-2 monoclonal antibody (IL-2mAb, JES6-1) in combatting demyelination during the late phase of stroke.

IL-2mAb or IgG isotype antibody (0.25 mg/kg) was injected intraperitoneally 2 and 48 hours after middle cerebral artery occlusion (MCAO) surgery. Infarct volume, peripheral immune cell infiltration, microglia activation, and myelin loss were measured by 2,3,5-triphenyte trazoliumchloride staining, immunofluorescence staining, flow cytometry, and Western blot. Intraperitoneal CD8 neutralizing antibody (15 mg/kg) was injected 1 day before MCAO surgery to determine the role of CD8⁺ T cells on demyelinating lesions.

IL-2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long-term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8⁺ T cells and peripheral activation of CD8⁺ T cells were both attenuated in IL-2 mAb-treated mice. The protection of IL-2mAb on demyelination was abolished in mice depleted of CD8⁺ T cell 1 week after stroke.

IL-2mAb preserved white matter integrity and improved long-term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8⁺ T cells are detrimental for demyelination after stroke and may be the major target of IL-2mAb posttreatment in the protection of white matter integrity after stroke.