The role of T helper 1 and T helper 2 lymphocyte subsets in the pathogenesis of experimental autoimmune uveoretinitis
CD4+ T cells can be subdivided on the basis of their lymphokine repertoire produced on activation resulting in TH1 like and TH2 like populations. The purpose of this study was to measure the intraocular expression of cytokines as a means of defining the CD4+ lymphocyte subsets present during the development of uveoretinitis. Lewis rats were immunised with retinal antigen and pertussis toxin resulting in early signs of disease activity evident by day 9 with increasing severity evident by day 12. Extensive clinical and histological damage was observed by day 14 with a reduction in severity through to end stage disease at day 24. In this study, the failure to establish pure populations of retinal antigen specific T lymphocyte cell lines and the observation of the lack of sensitivity of Northern hybridization to signals expressed at low levels resulted in the more sensitive technique of RT-PCR being utilized. Both IL2 and IFN mRNA expression was detected at all stages of disease with highest levels being present early in uveitis. In contrast IL4 mRNA levels increased with disease progression. This study suggests a pathogenic role for TH1 like cells and a protective role for TH2 like cells in this autoimmune disease. In order to provide an insight into alternative treatment strategies of the disease, immunomodulation of EAU was carried out using the immunosuppressive drugs CsA, FK506 and rapamycin and the resultant cytokine mRNA profiles examined. The results indicated that CsA and FK506 downregulated the TH1 response having suppressive effects on the levels of IL2 and IFN mRNA respectively. In contrast rapamycin was found to modulate the TH2 response enhancing IL4 levels. From this data, a drug based strategy employing rapamycin appears to be the most favourable approach.