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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3838-3846

IMMUNOBIOLOGY

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

Vincenzo Bronte, Elisa Apolloni, Anna Cabrelle, Roberto Ronca, Paolo Serafini, Paola Zamboni, Nicholas P. Restifo, and Paola Zanovello

From the Department of Oncology and Surgical Sciences, Padua University, Padova, Italy; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Apoptotic death of CD8+ T cells can be induced by a population of inhibitory myeloid cells that are double positive for the CD11b and Gr-1 markers. These cells are responsible for the immunosuppression observed in pathologies as dissimilar as tumor growth and overwhelming infections, or after immunization with viruses. The appearance of a CD11b+/Gr-1+ population of inhibitory macrophages (iMacs) could be attributed to high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vivo. Deletion of iMacs 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 these cells were positive for CD31, ER-MP20 (Ly-6C), and ER-MP58, markers characteristic of granulocyte/monocyte precursors. Importantly, although iMacs retained their inhibitory properties when cultured in vitro in standard medium, suppressive functions could be modulated by cytokine exposure. Whereas culture with the cytokine interleukin 4 (IL-4) increased iMac inhibitory activity, these cells could be differentiated into a nonadherent population 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 thus give rise to cells capable of either activating or inhibiting the function of CD8+ T lymphocytes, depending on the cytokine milieu that prevails during antigen-presenting cell maturation.

© 2000 by The American Society of Hematology.
 

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