Purchase this article with an account.
J. Chen, B.P. Vistica, S. Miyake, T. Yamamura, C.C. Chan, E.F. Wawrousek, I. Gery; The synthetic glycolipid "OCH", a stimulant of NKT cells, inhibits Th1 cell–mediated ocular inflammation, but enhances disease induced by Th2 cells. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2311.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Natural killer T (NKT) cells, a population of lymphocytes with immunomodulatory capacity, recognize glycolipids such as alpha galactosylceramide (a–GalCer) presented by the MHC class I–like molecule CD1d. "OCH", an analogue of a–GalCer, was shown to be able to stimulate NKT cells and inhibit induction of EAE (Miyamoto et al. Nature 2001, 413: 531). Here, we examined the effect of treatment with OCH on ocular inflammation induced in mice by either Th1 or Th2 cells. Methods: Th cells specific for hen egg lysozyme (HEL) were polarized in vitro into Th1 or Th2 populations by activation with HEL in the presence of type–specific cytokines and antibodies (Kim et al. IOVS 2002, 43:758). Ocular inflammation was induced by adoptive transfer of these Th1 or Th2 cells into recipient mice that express HEL in their eyes. The effect of OCH on ocular inflammation was examined by a single i.p. administration of OCH (150 µg/kg) to the recipient mice concurrently with the cell transfer. Mice were evaluated for disease by histological examination. Cytokine production by cultured lymphocytes was measured by ELISA. Results: Treatment of mice with OCH significantly inhibited the development of ocular inflammation induced by Th1 cells, but enhanced the disease induction by Th2 cells. In addition, treatment with OCH inhibited production of IFN–gamma by spleen cells in recipients of Th1 cells, but enhanced IL–4 production by splenocytes in Th2 cell recipients. Conclusions: These data show for the first time the effects of a NKT cell stimulant on the efferent limb of immuno–pathogenic processes. OCH inhibits the Th1 cell–induced process, but enhances the disease induced by Th2 cells. Our findings suggest that OCH might be useful for therapeutic intervention in human diseases characterized by Th1–mediated pathology.
This PDF is available to Subscribers Only