Effects of polyclonal immunoglobulins and other immunomodulatory agents on microglial phagocytosis of apoptotic inflammatory T-cells.
T-cell apoptosis in the CNS is an effective mechanism for the noninflammatory resolution of autoimmune T-cell infiltrates. Ingestion of apoptotic leukocytes by microglia results in an efficient clearance of the inflammatory infiltrate, followed by a profound downregulation of proinflammatory phagocyte immune functions. The effects of different immunomodulatory agents on Lewis rat microglial phagocytosis of apoptotic autologous thymocytes or myelin-basic protein (MBP)-specific, encephalitogenic T-cells were investigated using a standardized, light microscopical in vitro phagocytosis assay. Pretreatment of microglia with polyclonal 7S immunoglobulins (IVIg) decreased the phagocytosis of apoptotic thymocytes by 38.2% (p<0.0001). Also, immunoglobulin F(ab')(2) fragments decreased microglial phagocytosis, suggesting an Fc receptor-independent mechanism. Similar results were obtained using MBP-specific T-cells. Pretreatment of microglia with IFN-gamma increased the phagocytosis of apoptotic cells by 65.4%, which was to a large extent counteracted by IVIg. Glatiramer acetate (GLAT) did not exert an effect on microglial phagocytosis, while methylprednisolone (MP) induced microglial apoptosis in vitro. These results indicate that IVIg has a high potential to inhibit microglial phagocytosis of apoptotic inflammatory T-cells even under proinflammatory conditions and extend our view of the complex immunomodulatory effects of IVIg.
Chan
Andrew
A
Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Julius-Maximilians-University, D-97080, Würzburg, Germany. AndrewHKChan@hotmail.com
Papadimitriou
Christina
C
Graf
Wolfgang
W
Toyka
Klaus V
KV
Gold
Ralf
R
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D000068717:Glatiramer Acetate; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008775:Methylprednisolone / Q000494:pharmacology; D017628:Microglia / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology*
D007140:Immunoglobulin Fab Fragments; D016756:Immunoglobulins, Intravenous; D010455:Peptides; D000068717:Glatiramer Acetate; D007371:Interferon-gamma; D008775:Methylprednisolone