DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.
DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12-/- mice to experimental autoimmune encephalomyelitis (EAE). DAP12-/- mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNgamma by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.
Bakker
A B
AB
Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco 94143, USA.
Hoek
R M
RM
Cerwenka
A
A
Blom
B
B
Lucian
L
L
McNeil
T
T
Murray
R
R
Phillips
L H
LH
Sedgwick
J D
JD
Lanier
L L
LL
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage* / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D018390:Gene Targeting; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D051381:Rats; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; C571326:MOG protein, human; D008565:Membrane Proteins; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011971:Receptors, Immunologic; C110546:TYROBP protein, human