Immunological studies of chronic ocular toxoplasmosis: Up-regulation of major histocompatibility complex class I and transforming growth factor beta and a protective role for interleukin-6

A murine model was used to characterize the local immune and inflammatory r esponse during ocular toxoplasmosis. Major histocompatibility complex (MHC) class I, normally expressed at low levels in immune-privileged sites such as the eye, was up regulated during infection as determined by competitive reverse transcriptase (RT) PCR and immunocytochemistry for both beta2-micro globulin and the MHC class I heavy chain. However, the eyes of chronically infected mice also had increased levels of mRNA transcripts for transformin g growth factor beta, a cytokine associated,vith immune privilege and const itutively expressed in normal eyes. Transcripts for a number of inflammator y mediators, including interleukin-6 (IL-6), were increased during chronic infection. The role of IL-6 was further investigated by comparing disease p rogression and the development of the local immune response in wild-type (W T) and IL-6-deficient mice (IL-6(-/-) mice). Following infection, IL-6(-/-) mice developed more severe inflammation in the retina and vitreous humor c ompared,vith WT mice. This increased severity of disease aas associated wit h reduced ocular IL-1 alpha and increased tumor necrosis factor alpha mRNA production compared with WT mice. Moreover, the increased severity of disea se in IL-6(-/-) mice correlated with increased eye parasite burden as deter mined by RT-PCR for the Toxoplasma gondii bradyzoite-specific LDH2 gene. Th ese results demonstrate alterations to components of immune privilege as a result of ocular toxoplasmosis and a role far IL-6 in controlling parasite numbers and inflammation in the eye.