Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus

• Published in: Journal of rheumatology 2001-12, Vol.28 (12), p.2644-2649
• Main Authors: RIDER, Virginia, JONES, Stephanie, EVANS, Marilyn, BASSIRI, Hala, AFSAR, Zoka, ABDOU, Nabih I
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; CD3 Complex - immunology; CD40 Antigens - biosynthesis; CD40 Antigens - genetics; Cells, Cultured; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Estrogens - pharmacology; Female; Flow Cytometry; Humans; Ionomycin - pharmacology; Ionophores - pharmacology; Ligands; Lupus Erythematosus, Systemic - blood; Medical sciences; Middle Aged; Polymerase Chain Reaction; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; RNA, Messenger - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism
• ISSN: 0315-162X; 1499-2752

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.