V. Rider et al., Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus, J RHEUMATOL, 28(12), 2001, pp. 2644-2649
Objective. To examine the in vitro effects of estrogen on CD40 ligand (CD40
L) expression in peripheral blood T cells isolated from patients with syste
mic lupus erythematosus (SLE) and normal controls.
Methods. T cells from female patients with SLE and controls were cultured i
n serum-free medium without and with 2-fluoroestradiol. Some T cells were a
ctivated by further culture on anti-CD3 coated plates. Calcineurin was acti
vated in some T cells by culture in ionomycin. Cell surface CD40L was quant
itated by FACS analysis. mRNA expression was measured using semiquantitativ
e PCR.
Results. Lupus T cells cultured in medium containing 2-fluoroestradiol show
ed a significant (p = 0.04) increase in the amount of CD40L on the cell sur
face, but not in the number of positive cells, compared to the same T cells
cultured without estradiol. Estradiol did not significantly change CD40L e
xpression on the surface of T cells from normal women. In addition, the dif
ference in cell surface CD40L between T cells cultured without and with est
radiol 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 signi
ficant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen d
ependent increases in SLE T cell CD40L mRNA and cell surface protein were b
locked by the estrogen receptor antagonist ICI 182,780. SLE and normal T ce
lls pretreated with estradiol and cultured with ionomycin for 2 h to activa
te calcineurin showed no significant differences in CD40L mRNA.
Conclusion. These results suggest that estradiol, working through the estro
gen receptor, stimulates the expression of CD40L in unstimulated and activa
ted SLE T cells. Estradiol effects may be exerted on multiple regulatory st
eps that control CD40L expression. The estrogen dependent increase in CD40L
expression could hyperstimulate SLE T cells and thereby contribute to the
pathogenesis of SLE.