Alteration of CD39Â +Â Foxp3Â + CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment

•Mice treated with murine anti-CD52 are protected against EAE disease progression.•Synthesis of inflammatory cytokines is significantly suppressed following treatment.•Enhanced IL-10 in plasma of EAE mice indicate treatment effect in periphery.•Anti-CD52 treatment induces CD39 + regulatory T cells in EAE mice and MS patients.

While examining the therapeutic value of anti-CD52 antibody against EAE/MS, we identified a unique subset of CD39 + Tregs in repopulating GALT tissues, a major lymphoid reservoir, which was accompanied by amelioration of disease. Furthermore, anti-CD52 treatment leads to increased expression of BDNF, IL-10, and SMAD3 in the brains of EAE mice. This condition is associated with suppression of IL-17, a critical inflammatory factor in EAE/MS progression. Additionally, we found elevated levels of CD4 + CD39 + Tregs in PBMCs of RRMS patients treated with humanized anti-CD52 mAb. Thus, anti-CD52 can affect multiple immune mediated pathways involved in the pathogenesis of EAE/MS.

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