Suppressor role of rat CD8+CD45RClow T cells in experimental autoimmune uveitis (EAU).
To determine whether decreased regulatory T cell activity contributes to the pathogenesis of recurrent experimental autoimmune uveitis (EAU), we compared the immunoregulatory activity of CD8+CD45RClow T cells isolated from rats that had recovered from acute EAU with those from rats with the progressive, recurrent disease. Our results showed that CD8+CD45RClow T cells isolated from the recovered rats showed suppressive activity in vitro, whereas those from rats with progressive, recurrent EAU do not. Depletion of CD8+CD45RClow T cells from T cells used for adoptive transfer of EAU increased the pathogenic activity of the T cells. Co-transfer of CD8+CD45RClow T cells with uveitogenic T cells prevented the relapse of disease in the recipient rats. The suppressive CD8+CD45RClow T cells expressed increased levels of Foxp3 after stimulation in vitro with the autoantigen, and inhibited the production of IFN-gamma by autoreactive T cells. Our data indicate that the decreased suppressive activity of CD8+CD45RClow T cells is correlated with disease development in this autoimmune disease. Further studies on the biology of this T cell population should provide much needed insights into disease pathogenesis.
Han
Gencheng
G
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Shao
Hui
H
Peng
Yong
Y
Zhang
Ping
P
Ke
Yan
Y
Kaplan
Henry J
HJ
Sun
Deming
D
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000150:complications / Q000276:immunology* / Q000473:pathology*
D007371:Interferon-gamma; D017493:Leukocyte Common Antigens