Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable ofactivating or suppressing CD8(+) T cells

Apoptotic death of CD8(+) T cells can be induced by a population of inhibit ory myeloid cells that are double positive for the CD11b and Gr-1 markers. These cells are responsible for the immunosuppression observed in pathologi es as dissimilar as tumor growth and overwhelming infections, or after immu nization with viruses. The appearance of a CD11b(+)/Gr-1(+) population of i nhibitory macrophages (iMacs) could be attributed to high levels of granulo cyte-macrophage colony-stimulating factor (GM-CSF)in vivo. Deletion of iMac s in vitro or in vivo reversed the depression of CD8(+) T-cell function. We isolated iMacs from the spleens of immunocompromised mice and found that t hese cells were positive for CD31, ER-MP20 (Ly-6C), and ER-MP58, markers ch aracteristic of granulocyte/monocyte precursors. Importantly, although iMac s retained their inhibitory properties when cultured in vitro in standard m edium, suppressive functions could be modulated by cytokine exposure. Where as culture with the cytokine interleukin 4 (IL-4) increased iMac inhibitory activity, these cells could be differentiated into a nonadherent populatio n of fully mature and highly activated dendritic cells when cultured in the presence of IL-4 and GM CSF. A common CD31(+)/CD11b(+)/Gr-1(+) progenitor can th us give rise to cells capable of either activating or inhibiting the function of CD8(+) T lymphocytes, depending on the cytokine milieu that pr evails during antigen-presenting cell maturation. (C) 2000 by The American Society of Hematology.