PD-L1 (B7-H1) regulation in zones of axonal degeneration.
Fibre tract injury evokes recruitment of antigen-presenting- and T cells, but does not cause autoimmune demyelination. This implies that immune tolerance to myelin is actively maintained or readily re-established. Using entorhinal cortex lesion (ECL) to induce axonal degeneration in the hippocampus of adult mice, we studied the induction of B7-H1 (PD-L1) in zones of axonal degeneration. This member of the B7-family has been shown to be expressed on parenchymal cells of various organs, where it strongly down-modulates the activity of T cells. Real-time reverse transcriptase (RT)-PCR revealed low mRNA levels in brain compared to lung and spleen under normal conditions. After ECL, a twofold increase could be observed. Immunocytochemistry revealed astrocytes as source of B7-H1, while immune positive microglia were not detected. Thus, axonal degeneration induces astrocytes to express B7-H1, a potent inhibitor of effector T cells.
Lipp
Michael
M
Institute of Cell Biology and Neurobiology, Department Exp. Neuroimmunology, Charité, 10098 Berlin, Germany.
Brandt
Christine
C
Dehghani
Faramarz
F
Kwidzinski
Erik
E
Bechmann
Ingo
I
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D001253:Astrocytes / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001369:Axons / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D060890:B7-H1 Antigen; D001930:Brain Injuries / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology* / Q000503:physiopathology; D004660:Encephalitis / Q000276:immunology* / Q000503:physiopathology; D018728:Entorhinal Cortex / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000276:immunology / Q000503:physiopathology; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014855:Wallerian Degeneration / Q000276:immunology* / Q000503:physiopathology