IFN-gamma up-regulation of IL-12 beta 2 receptor is associated with experimental autoimmune uveitis susceptible B10.A mice, but not in EAU resistant BALB/c mice.

ABSTRACT

IFN-gamma production is a hallmark of Th1 response, and IFN-gamma has multiple roles in Th1 development, depending on the experimental conditions. In this study, the correlation between IFN-gamma and interleukin 12 receptor beta2 (IL-12R beta 2) expression was investigated in experimental autoimmune uveitis (EAU) susceptible B10.A and resistant BALB/c mice. B10.A mice expressed high IL-12R beta 2 on T cells either in the disease target eyes or draining lymph node cells (LNC), and its expression correlated with the Th1-type response. In contrast, BALB/c mice only expressed minimal IL-12R beta 2 in draining LNC and had lower Th1-response. B10.A mice produced more IFN-gamma and generated a higher number of Th1 cells than that of BALB/c in the draining LNC. Furthermore, IL-12R beta 2 expression and STAT4 signaling were inhibited by anti-IFN-gamma mAb in the cultured draining LNC from B10.A mice, but enhanced by adding exogenous IFN-gamma in the cultured cells from BALB/c mice. The IL-12R beta 2 expression on Th1 cells from draining LNC was increased in the presence of IL-12 and IFN-gamma. In conclusion, IFN-gamma production correlated with IL-12R beta 2 expression on Th1-cells and IFN-gamma had a potential to regulate IL-12R beta 2 expression in vivo. This regulatory mechanism might be involved in EAU induction.