Establishment and characterization of a murine CD4+ T cell line and clone that induce experimental autoimmune uveoretinitis in B10.A mice.

Abstract

B10.A mice develop experimental autoimmune uveoretinitis after active immunization with the interphotoreceptor retinoid-binding protein (IRBP). CD4+ T cells play an important role in the development of the disease. In this study we have isolated and characterized a CD4+ T cell line and a T cell clone that induce experimental autoimmune uveoretinitis when transferred into naive B10.A mice. The cell line was isolated from draining lymph nodes of IRBP-immunized animals by repeated cycles of IRBP stimulation. The line was shown to be pathogenic after 4 rounds of in vitro stimulation with IRBP at 5 x 10(6) cells/mouse. A T cell clone derived from this line by limiting dilution was shown to be pathogenic when the same number of cells was injected; incidence and severity of disease, however, were much lower. After 16 rounds of IRBP-specific stimulation the cell line was pathogenic at 10(5) cells/mouse. Analysis of the V beta repertoire revealed that at this point the line was mostly composed of V beta 8.2- and V beta 6-positive cells (> 80% of the population). The uveitogenic clone expressed V beta 8.2. Both the T cell line and the clone elaborated an unrestricted lymphokine profile in vitro. However, when these cells were adoptively transferred into naive recipients, mRNA isolated from the uveitic retina showed only Th1 type cytokines. These data help to characterize the nature of pathogenic cells involved in ocular autoimmunity.