Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development.
Myeloid-derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how DC development and MDSC suppressor activity both generated from myeloid precursor cells are regulated. Here, we show that the combined treatment of BM-derived MDSC with LPS plus IFN-gamma inhibited the DC development but enhanced MDSC functions, such as NO release and T-cell suppression. This was not observed by the single treatments in vitro. In the spleens of healthy mice, we identified two Gr-1(low)CD11b(high)Ly-6C(high)SSC(low)Mo-MDSC and Gr-1(high)CD11b(low)PMN-MDSC populations with suppressive potential, whereas Gr-1(high)CD11b(high) neutrophils and Gr-1(low)CD11b(high)SSC(low) eosinophils were not suppressive. Injections of LPS plus IFN-gamma expanded these populations within the spleen but not LN leading to the block of the proliferation of CD8(+) T cells. At the same time, their capacity to develop into DC was impaired. Together, our data suggest that spleens of healthy mice contain two subsets of MDSC with suppressive potential. A two-signal-program through combined LPS and IFN-gamma treatment expands and fully activates MDSC in vitro and in vivo.
Greifenberg
Verena
V
Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
Ribechini
Eliana
E
Rössner
Susanne
S
Lutz
Manfred B
MB
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D039481:CD11b Antigen; D016207:Cytokines; C503133:Gr-1 protein, mouse; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; D009569:Nitric Oxide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin