TY - JOUR T1 - Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. JF - The Journal of Rheumatology JO - J Rheumatol SP - 2644 LP - 2649 VL - 28 IS - 12 AU - V Rider AU - S Jones AU - M Evans AU - H Bassiri AU - Z Afsar AU - N I Abdou Y1 - 2001/12/01 UR - http://www.jrheum.org/content/28/12/2644.abstract N2 - OBJECTIVE: To examine the in vitro effects of estrogen on CD40 ligand (CD40L) expression in peripheral blood T cells isolated from patients with systemic lupus erythematosus (SLE) and normal controls. METHODS: T cells from female patients with SLE and controls were cultured in serum-free medium without and with 2-fluoroestradiol. Some T cells were activated by further culture on anti-CD3 coated plates. Calcineurin was activated in some T cells by culture in ionomycin. Cell surface CD40L was quantitated by FACS analysis. mRNA expression was measured using semiquantitative PCR. RESULTS: Lupus T cells cultured in medium containing 2-fluoroestradiol showed a significant (p = 0.04) increase in the amount of CD40L on the cell surface, but not in the number of positive cells, compared to the same T cells cultured without estradiol. Estradiol did not significantly change CD40L expression on the surface of T cells from normal women. In addition, the difference in cell surface CD40L between T cells cultured without and with estradiol was significantly greater (p = 0.048) on SLE than on normal T cells. Culture of SLE T cells in medium containing 2-fluoroestradiol followed by T cell receptor (TCR) activation for 2 h using anti-CD3 resulted in a significant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen dependent increases in SLE T cell CD40L mRNA and cell surface protein were blocked by the estrogen receptor antagonist ICI 182,780. SLE and normal T cells pretreated with estradiol and cultured with ionomycin for 2 h to activate calcineurin showed no significant differences in CD40L mRNA. CONCLUSION: These results suggest that estradiol, working through the estrogen receptor, stimulates the expression of CD40L in unstimulated and activated SLE T cells. Estradiol effects may be exerted on multiple regulatory steps that control CD40L expression. The estrogen dependent increase in CD40L expression could hyperstimulate SLE T cells and thereby contribute to the pathogenesis of SLE. ER -