Role of reactive oxygen species in gender-associated autoimmunity (83.15)

Abstract

Abstract Gender-bias exists in proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) in that both male and female SJL mice develop disease but only females show chronic relapses and their underlying mechanisms are unknown. It has been shown that the reactive oxygen species (ROS) play a role in the mediation of autoimmune diseases, but the recent evidence suggests that ROS can suppress autoimmune responses. We hypothesize that T cell-derived ROS are critical to the maintenance of self-tolerance and favor developing resistance to autoimmunity in male mice. To address this hypothesis, we used PLP 139-151-specific T cell receptor (5B6) transgenic (tg) mice and measured ROS production in activated 5B6 T cells by flow cytometry using CM-H2DCFDA as an ROS indicator. Unexpectedly, we found that T cells from female mice produced two fold more ROS when compared to males. We verified these differences by evaluating mRNA expression of oxidative and anti-oxidative defense genes in 5B6 tg T cells and PLP 139-151-specific T cells sorted from immunized wild type (wt) SJL mice by using PLP 139-151 tetramers. TaqMan PCR analysis revealed that interleukin-22 mRNA, a cytokine implicated in ROS metabolism and EAE pathogenesis was increased by three fold in T cells obtained from tg or wt female mice. The data suggests that sex steroids and T cell-derived cytokines have a role in the maintenance of redox homeostasis in autoreactive T cells and T cell tolerance.