Purpose. We have shown that apoptotic cell death induced by FasL expressed in the eye was required to establish immune deviation following anterior chamber (AC) injection of antigen. Here we examine the mechanisms by which this takes place. Methods. C57BL/6 (B6) or IL-10 KO were injected in the anterior chamber (AC) with TNP-spl. Mice were examined for the presence of intraocular IL-10 and the establishment of immune deviation. TNP-spl were induced to undergo apoptosis by yirradiation, and then cultured with adherent peritoneal exudate cells (PEC) for 1 hr, Adherent cells were harvested and transferred i.v. to naive recipients to assess immune deviation. Results. Within two hours of AC injection, IL-10 is made by inflammatory cells in the eye prior to their death by apoptosis. The importance of early IL-10 production was demonstrated by showing that TNP-spl from IL-10 KO mice do not induce immune deviation when injected in the AC of normal mice. Adherent PEC cultured with apoptotic, but not necrotic, TNP-spl induced immune deviation when transferred to naive mice. Conclusions. Our data show that antigen presenting cells that have processed apoptotic cells containing IL-10 may induce the development of Th2 type CD4 T-cells leading to the inhibition of Thl CD44 T-cells and the establishment of immune deviation. This may be a result of antigen presentation in the absence of co-stimulators such as B7-1 and B7-2. The results provide an explanation for the requirement for apoptotic cell death in the eye to induce systemic immune deviation.
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Dec 1 1997|