Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed.
Cells of the macrophage lineage are required to cope with bacterial infection and to serve as APC for T lymphocytes. Among the regulatory factors limiting the macrophage response to infection and the expansion of Ag-specific T cells, IL-10 has received recent attention. On monocytes/macrophages, IL-10 has been shown to inhibit the intracellular killing of bacteria, the secretion of cytokines, and the expression of MHC molecules. In the present study we have examined the effect of IL-10 on different APC obtained from the central nervous system. Both, astrocytes and microglial cells are in a resting state and require activation signals to express MHC class II and cytokine genes. Whereas IL-10 profoundly inhibits the IFN-gamma-induced expression of MHC class II Ag on microglial cells, it had no such effects on astrocytes. Nevertheless, IL-10 suppressed the MHC class II- and Ag-dependent proliferative response of T cells in the presence of both types of APC. As shown by the use of anti-IL-10 Abs, endogenously produced IL-10 influenced the function of microglia but not of astrocytes to serve as APC. IL-10 significantly inhibited the LPS-induced production of granulocyte-macrophage-CSF, macrophage-CSF, and IL-6 by both astrocytes and microglial cells. In contrast, the secretion of these cytokines by the two glial cell population was not altered by IL-10 when IL-1 beta, TNF-alpha, or viruses were used as stimuli.
Frei
K
K
Section of Clinical Immunology, University Hospital Zürich, Switzerland.
Lins
H
H
Schwerdel
C
C
Fontana
A
A
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016753:Interleukin-10