Gene expression profile of preclinical arthritis and its modulation by antigen-induced tolerance

During the course of adjuvant arthritis, maximal changes in gene expression were observed at the incubation phase. A major group of genes affected was related to immune activity. Tolerance induction by mycobacterial heat-shock protein 65 (Bhsp65), the disease-related antigen, caused upregulation of a large number of genes. These included immune activity genes as well as cell proliferation-related genes. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. The draining lymph node cells (LNC) were harvested from arthritic rats at different phases of adjuvant arthritis (incubation,peak and recovery). Also tested were LNC of naïve rats. LNC were tested ex vivo. Total RNA isolated from LNC was used for testing with affymetrix gene chip following manufacturer's instructions. Similarly, LNC of Bhsp65-tolerized rats harvested at incubation phase were tested with or without Bhsp65 restimulation in vitro. LNC of arthritic rats in incubation phase were similarly restimulated with Bhsp65 in vitro as controls, and the results compared with that of the tolerized rats.