Prevention of autoimmunity by induction of cutaneous tolerance.
Autoimmune gastritis develops in 20-60% of BALB/c mice following thymectomy at 3 days after birth (3dnTx). Previously we identified the gastric H+/K+ ATPase as the causative autoantigen and mapped the immunoreactive T cell epitope to a carboxyl-terminal peptide on the gastric H+/K+ ATPase beta subunit. Here we show that autoimmune gastritis can be suppressed by immunizing 3dnTx mice through neonatal skin with the beta subunit peptide, in combination with the contact sensitizer TNCB. When spleen cells were transferred from suppressed mice to nude mice a proportion of recipient mice developed gastritis. These results indicate that pathogenic T cells were still present in the 3dnTx mice but the absence of gastritis indicates that their activity can be regulated following induction of cutaneous tolerance by immunizing through neonatal skin. We propose that cutaneous tolerance is induced through mediation of immature Langerhans cells in neonatal skin and that this tolerance prevented the autoreactivity of pathogenic T cells. This procedure will have implications for strategies to suppress autoimmunity.
Woods
G M
GM
Discipline of Pathology, University of Tasmania, Hobart, Australia.
Chen
Y P
YP
Dewar
A L
AL
Doherty
K V
KV
Toh
B H
BH
Muller
H K
HK
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D015551:Autoimmunity / Q000276:immunology*; D002452:Cell Count; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000517:prevention & control; D005756:Gastritis / Q000276:immunology / Q000517:prevention & control; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010853:Picryl Chloride / Q000009:adverse effects / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013934:Thymectomy
D001323:Autoantibodies; D001324:Autoantigens; D017506:H(+)-K(+)-Exchanging ATPase; D010853:Picryl Chloride