Glucocorticoids induce corneal allograft tolerance through expansion of monocytic myeloid-derived suppressor cells

Abstract

Glucocorticoids (GCs) are the most widely used drugs to prevent transplant rejection; however, it is not yet clear how GCs induce immune tolerance in transplantation. Here, we demonstrate that GCs induce tolerance to corneal allografts in mice through expansion of MHC class II(-)CD11b(+)Ly6C(+) monocytes in the bone marrow and mobilization of the cells to spleen, draining lymph nodes, and graft site. The GC-induced CD11b(+)Ly6C(+) monocytes inhibited T cell proliferation in vitro, and adoptive transfer of the cells improved the survival of corneal allografts. Depletion of CD11b(+)Ly6C(+) cells in mice during GC treatment abrogated the effects of GCs in prevention of immune rejection. Together, the results identify monocytic myeloid-derived suppressor cells as crucial mediators of the GC-induced tolerance in transplantation.