Differentiation driven by granulocyte-macrophage colony-stimulating factor endows microglia with interferon-gamma-independent antigen presentation function.
The antigen presentation function of microglial cells was analyzed after differentiation in neonatal mouse brain cell cultures supplemented either with macrophage (M) or granulocyte/macrophage (GM) colony-stimulating factor (CSF). The cells separated from concomitant astrocytes in both culture systems turned out to exhibit cytological characteristics of macrophages and bore MAC-1 and F4/80 markers in a similar way. When comparatively tested for accessory cell function, only microglia developed with GM-CSF were able to efficiently induce antigen-directed proliferation of a series of helper T cell lines representing both the TH1 and TH2 subtype. Antigenic T cell activation by this microglia population was performed without prior stimulation and exceeded that of M-CSF-dependently grown microglial cells, even if those had been pretreated with interferon-gamma (IFN-gamma). In contrast to such difference in function, low cell surface expression of MHC class II or intercellular adhesion molecule-1 determinants proved to coincide in both populations. Correlating with the capacity for antigen presentation, expression of membrane-bound interleukin-1 (IL1)--a costimulatory signal for TH2 cells--was augmented significantly in GM-CSF-grown microglia. In parallel, the interaction only of this microglia population with a selected TH1 cell line was accompanied by maximal release of T cell-stimulating factor, a cytokine recently identified as an IL1-analogous second signal for TH1 cells. Thus, a developmental process is suggested which produces a form of microglia specialized in antigen presentation and thereby acting uncoupled from IFN-gamma.
Fischer
H G
HG
Institut für Medizinische Mikrobiologie und Virologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Nitzgen
B
B
Germann
T
T
Degitz
K
K
Däubener
W
W
Hadding
U
U
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001921:Brain / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor