Identification of Th2-type suppressor T cells among in vivo expanded ocular T cells in mice with experimental autoimmune uveoretinitis.
Experimental autoimmune uveoretinitis (EAU), which is a T cell mediated organ specific autoimmune disease, is induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in susceptible strains of mice. It has been found that IRBP-derived peptide 518-529 (p518-529) generates Th2-type responses and inhibits IRBP-induced EAU, indicating that the p518-529 might be an epitope for suppressor T cells in IRBP-induced EAU. First, we observed that there were T cells producing the Th2 type cytokines such as IL-4 and IL-10 in late phase of EAU. Furthermore, to examine whether p518-529-reactive T cells expand in the eye during EAU, T cell receptor (TCR) of ocular T cells was compared with that of p518-529 reactive T cells in spleen from mice with EAU by PCR-single strand conformation polymorphism (PCR-SSCP) and nucleotide sequence analysis. SSCP and sequence analyses indicated that p518-529 reactive TCR BV10+ T cells bearing amino acid motif(PWG) and TCR BV13+ T cells bearing amino acid motif(PGLGGY) in their complementary-determining region 3 (CDR3) region were clonally expanding in ocular tissues on day 28 after immunization, although these T cells were not detected on day 14. These findings demonstrate that p518-529 reactive Th2-type T cells expand oligoclonally in the uveitic eyes in the late stage of EAU and may function as Th2-type suppressor T cells for improvement of the disease.
Keino
H
H
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan. h-keino@qj8.so-net.ne.jp
Takeuchi
M
M
Suzuki
J
J
Kojo
S
S
Sakai
J
J
Nishioka
K
K
Sumida
T
T
Usui
M
M
D020816:Amino Acid Motifs; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005136:Eye Proteins; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D012160:Retina / Q000276:immunology / Q000473:pathology; D012173:Retinitis / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology*; D014602:Uvea / Q000276:immunology / Q000473:pathology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D001324:Autoantigens; D018076:DNA, Complementary; D000939:Epitopes; D005136:Eye Proteins; D007371:Interferon-gamma; D016753:Interleukin-10; D015847:Interleukin-4; D010446:Peptide Fragments; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C427844:interphotoreceptor retinoid binding protein (518-529)