Conversion of Monophasic to Recurrent Autoimmune Disease by Autoreactive T Cell Subsets

Abstract

Autoimmune uveitis has been elicited in susceptible rodents by several ocular-specific Ags. In most of these animal models the induced uveitis is acute and monophasic. Because recurrent uveitis poses the highest risk for blinding ocular complications in human disease, a spontaneous relapsing animal model would be most helpful in understanding the disease pathogenesis. In our current study we have observed that the adoptive transfer of interphotoreceptor retinoid-binding protein residues 1177–1191-specific T cells to naive Lewis rats induced a chronic relapsing disease, in contrast to the monophasic disease induced by immunization with interphotoreceptor retinoid-binding protein residues 1177–1191 emulsified in CFA. The chronic relapsing uveitis induced by autoreactive T cell subsets is dependent on the number of autoreactive T cells generated as well as their activation status. Our study documented a spontaneous model of recurrent uveitis in the rat, which should assist us in the study of disease pathogenesis and the design of specific therapy.

Suppressor role of rat CD8+CD45RClow T cells in experimental autoimmune uveitis (EAU)

“…As we previously reported, Lewis rats immunized with the uveitogenic peptide R16 develop an acute and monophasic uveitis, showing overt clinical symptoms at 8-9 days post-immunization (p.i.) which persist for 4-5 days and subside subsequently, whereas the disease induced by adoptive transfer of in vitro activated IRBP-specific T cells develop an acute uveitis with several recurrences (Shao et al, 2003b). We found that in monophasic EAU rats, the numbers of CD8 + CD45RC low T cells were significantly increased in recovered phase of disease ( Fig.…”

“…(Sun et al, 1988b, Sun et al, 1988a. To determine whether regulatory T cell lines express different levels of CD45RC, we compared the CD45RC expression of an encephalitogenic T cell line, S1 (Sun et al, 1988b, Sun et al, 1988a, a uveitogenic T cell line, S22 (Shao et al, 2003b), and the anti-S1 line (Sun et al, 1988b, Sun et al, 1988a. As shown in Fig.…”

“…Animal Model of EAU-The induction of uveitis in Lewis rats by immunization with peptide R16 has been described previously (Shao et al, 2004, Shao et al, 2003a, Shao et al, 2003b. Briefly, the rats were immunized subcutaneously with 200 μl of an emulsion containing 50 μg of R16 and 500 μg of Mycobacterium tuberculosis H37Ra (Difco, Detroit, MI) in incomplete Freund's adjuvant (Sigma, St Louis), distributed over six spots on the tail base and flank.…”

“…Previous studies in our laboratory have established two prototypic rat EAU models. In one, the disease is monophasic and the animal recovers completely after an acute episode lasting for 5-7 days (designated as recovered rats), while, in the other, the disease is progressive and recurrent and the animals have repeated exacerbations of disease for at least two-three months (Shao et al, 2003b). The availability of these two disease models provides us with a good opportunity to determine whether disease progression is caused by increased activity of pathogenic T cells or decreased activity of suppressor T cells.…”

The Net Effect of Costimulatory Blockers Is Dependent on the Subset and Activation Status of the Autoreactive T Cells

“…Both the number and the activation status of autoreactive T cells are crucial for their pathogenic activity (14,17,18). In both experimental autoimmune encephalomyelitis and EAU, transfer of as few as 1 ϫ 10 6 newly activated autoreactive T cells readily induces disease, whereas transfer of 100 times as many nonactivated T cells does not (H. Shao and D. Sun, unpublished observation).…”