GM-CSF promotes differentiation of human dendritic cells and T lymphocytes toward a predominantly type 1 proinflammatory response.
OBJECTIVE
We recently demonstrated that patients with high levels of circulating dendritic cells (DC) and interleukin (IL)-12 are associated with reduced cancer relapse after hematopoietic stem cell transplantation. Identifying a growth factor that can promote these immune functions may have beneficial anti-tumor effects. We investigated the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) induces IL-12 production and polarizes T lymphocytes toward a proinflammatory response.


METHODS
Peripheral blood mononuclear cells (PBMC), T lymphocytes, and antigen-presenting cells (APC) were cultured with GM-CSF and compared with no growth factors (control), G-CSF, or both GM-CSF and G-CSF. Cells were matured with either lipopolysaccharide or lectin (phytohemagglutinin). Type 1 and type 2 cytokines were measured by enzyme-linked immunosorbent assay. Induction of allogeneic T-lymphocyte proliferation induced by GM-CSF-stimulated APC was measured by mixed lymphocyte reaction. DC were measured by flow cytometry.


RESULTS
Levels of type 1 (IL-12, interferon-gamma, tumor necrosis factor-alpha) cytokines increased while type 2 (IL-10 and IL-4) cytokines decreased after stimulation of PBMC, T lymphocytes, and APC with GM-CSF. APC treated with GM-CSF induced higher proliferation of allogeneic T cells. CD11c and CD123-positive DC proliferated after exposure to GM-CSF. Both subtypes of DC (DC1 and DC2) were increased by GM-CSF.


CONCLUSIONS
GM-CSF induces production of type 1 proinflammatory cytokines by human PBMC, T lymphocytes, and APC. Type 2 cytokines are downregulated by GM-CSF and proliferation of allogeneic T cells is increased. These results demonstrate the potential for GM-CSF as a clinical agent for immune stimulation.
Eksioglu
Erika A
EA
Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL 32611, USA.
Mahmood
Syed S
SS
Chang
Myron
M
Reddy
Vijay
V
D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018664:Interleukin-12 / Q000502:physiology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D008070:Lipopolysaccharides; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor