A suppressive oligodeoxynucleotide inhibits ocular inflammation.
Synthetic oligodeoxynucleotides (ODN) expressing 'suppressive' TTAGGG motifs down-regulate a variety of proinflammatory and T helper type 1 (Th1)-mediated pathological immune responses. The ability of the archetypal suppressive ODN A151 to inhibit ocular inflammation was examined in two murine models: experimental autoimmune uveitis, induced by immunization with a retinal antigen, interphotoreceptor retinoid-binding protein (IRBP) and adoptively transferred ocular inflammation, induced by transferring Th1 cells specific to hen egg lysozyme (HEL) into recipient mice that express HEL in their eyes. A151 treatment suppressed the inflammation in both models. In addition, A151 inhibited IRBP-specific cytokine production and lymphocyte proliferation in mice immunized with IRBP. These findings suggest that suppressive ODN affects both afferent and efferent limbs of the immunopathogenic process and may be of use in the treatment of autoimmune ocular inflammation.
Fujimoto
C
C
Laboratories of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1857, USA.
Klinman
D M
DM
Shi
G
G
Yin
H
H
Vistica
B P
BP
Lovaas
J D
JD
Wawrousek
E F
EF
Igarashi
T
T
Chan
C-C
CC
Gery
I
I
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009113:Muramidase / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D012177:Retinol-Binding Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000637:transplantation; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D009113:Muramidase; D009838:Oligodeoxyribonucleotides; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C421864:hen egg lysozyme