Peripheral monocytes are short-lived and are replenished from hematopoietic
stem cells whose proliferation is believed to be confined to the bone marr
ow. Human peripheral monocytes are assumed not to be able to proliferate. I
n this study we show that CD137 (ILA/4-IBB), a member of the tumor necrosis
factor receptor family, induces a widespread and profound proliferation of
human peripheral monocytes, Macrophage colony-stimulating factor and granu
locyte-macrophage colony-stimulating factor are essential, but not sufficie
nt for proliferation. Additional soluble autocrine factors induced by CD137
are required. Induction of proliferation is mediated via reverse signaling
through a CD137 ligand, expressed constitutively by peripheral monocytes.
The ability of CD137 to induce proliferation in human peripheral monocytes
is not shared by any other known molecule, (C) 1999 by The American Society
of Hematology.