Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells.
In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we report that anti-DEC205-mediated delivery of the self-peptide proteolipid protein (PLP)139-151 to DCs ameliorated clinical symptoms in the PLP-induced SJL model of experimental autoimmune encephalomyelitis. Splenocytes from treated mice were anergized to PLP139-151, and IL-17 secretion was markedly reduced. Moreover, we show directly, using transgenic CD4(+) Vβ6(+) TCR T cells specific for PLP139-151, that, under the conditions of the present experiments, these cells also became anergic. In addition, evidence for a CD4(+) T cell-mediated suppressor mechanism was obtained.
Stern
Joel N H
JN
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. jstern@fas.harvard.edu
Keskin
Derin B
DB
Kato
Zenichiro
Z
Waldner
Hanspeter
H
Schallenberg
Sonja
S
Anderson
Ana
A
von Boehmer
Harald
H
Kretschmer
Karsten
K
Strominger
Jack L
JL
D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D020381:Interleukin-17; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C435023:myelin proteolipid protein (139-151)