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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.
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