Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells.
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. (Blood. 2000;96:3838-3846)
Bronte
V
V
Department of Oncology and Surgical Sciences, Padua University, Padova, Italy. vbronte@ux1.unipd.it
Apolloni
E
E
Cabrelle
A
A
Ronca
R
R
Serafini
P
P
Zamboni
P
P
Restifo
N P
NP
Zanovello
P
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes; D007165:Immunosuppression Therapy; D015847:Interleukin-4 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus
D015415:Biomarkers; D016207:Cytokines; D007519:Isoantigens; D016177:Macrophage-1 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor