Antigens expressed by myelinating glia cells induce peripheral cross-tolerance of endogenous CD8+ T cells.
Auto-reactivity of T cells is largely prevented by central and peripheral tolerance. Nevertheless, immunization with certain self-antigens emulsified in CFA induces autoimmunity in rodents, suggesting that tolerance to some self-antigens is not robust. To investigate the fate of nervous system-specific CD8(+) T cells, which only recently came up as being important contributors for MS pathogenesis, we developed a mouse model that allows inducible expression of lymphocytic choriomeningitis virus-derived CD8(+) T-cell epitopes specifically in oligodendrocytes and Schwann cells, the myelinating glia of the nervous system. These transgenic CD8(+) T-cell epitopes induced robust tolerance of endogenous auto-reactive T cells, which proved thymus-independent and was mediated by cross-presenting bone-marrow-derived cells. Immunohistological staining of secondary lymphoid organs demonstrated the presence of glia-derived antigens in DC, suggesting that peripheral tolerance of CD8(+) T cells results from uptake and presentation by steady state DC.
Schildknecht
Anita
A
Institute of Experimental Immunology, Zurich, Switzerland. anita_schildknecht@bluewin.ch
Probst
Hans Christian
HC
McCoy
Kathy D
KD
Miescher
Iris
I
Brenner
Corinne
C
Leone
Dino P
DP
Suter
Ueli
U
Ohashi
Pamela S
PS
van den Broek
Maries
M
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001117:Arenaviridae Infections / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism; D012583:Schwann Cells / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology
D000941:Antigens; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma