Anti-CD52 blocks EAE independent of PD-1 signals and promotes repopulation dominated by double negative T cells and newly generated T and B cells.

: Lymphocyte depletion using anti-CD52 antibody effectively reduces relapses of multiple sclerosis (MS). To begin to understand what mechanisms might control this outcome, we examined the effect of a murine-CD52 specific monoclonal antibody on the depletion and repopulation of immune cells in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. We tested whether the tolerance-promoting receptor PD-1 is required for disease remission post anti-CD52; and found that PD-1 deficient mice with a more severe EAE were nevertheless effectively treated with anti-CD52. Anti-CD52 increased the proportions of newly generated T cells and DN T cells, while reducing newly generated B cells; the latter effect being associated with a higher expression of CD52 by these cells. In the longer-term, anti-CD52 caused substantial increases in the proportion of newly generated lymphocytes and DN T cells, in mice with EAE. Thus, the rapid repopulation of lymphocytes from central lymphoid organs post anti-CD52 may limit further disease. Furthermore, these data identify DN T cells, a subset with immunoregulatory potential, as a significant hyper-repopulating subset following CD52 mediated depletion. This article is protected by copyright. All rights reserved.