Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis.
OBJECTIVE
To investigate whether supplementation of natural CD4+CD25+ regulatory T cells ameliorates mouse experimental autoimmune uveoretinitis (EAU) induced by CD4+ T cell-dependent interphotoreceptor retinoid-binding protein (IRBP).


METHODS
C57BL/6 mice were immunised with human interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP(1-20)), and IRBP(1-20)-sensitised T cells were obtained. CD4+CD25+ T cells derived from naive mice were cocultured with IRBP(1-20)-sensitised T cells, and their proliferation responses and cytokine production were measured. In addition, CD4+CD25+ T cells were transferred intravenously into mice 7 or 15 days after immunisation with IRBP(1-20), and the severity of EAU and T cell proliferation responses were evaluated.


RESULTS
CD4+CD25+ regulatory T cells effectively inhibited both the proliferation of, and interleukin (IL)2, IL5 and interferon (IFN)gamma production by, IRBP(1-20)-sensitised T cells. Adoptive transfer of CD4+CD25+ regulatory T cells to IRBP(1-20)-immunised mice conferred considerable protection from EAU development and inhibition of T cell proliferation responses to IRBP(1-20).


CONCLUSIONS
These findings show that natural CD4+CD25+ regulatory T cells possess the ability to inhibit activation of IRBP-reactive T cells that have been already sensitised in vivo, and adoptive transfer of these cells ameliorates EAU even in the effector phase. Supplementation of natural CD4+CD25+ regulatory T cells may have therapeutic potential for effective treatment of uveitis.
Keino
H
H
Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Takeuchi
M
M
Usui
Y
Y
Hattori
T
T
Yamakawa
N
N
Kezuka
T
T
Sakai
J-I
JI
Usui
M
M
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012173:Retinitis / Q000276:immunology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C498833:Foxp3 protein, mouse