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.
Lupus monocytes clearly overexpressed CD40L comparing to healthy and disease-control monocytes, and, similarly to lupus T cells, displayed a prominent resistance to CsA inhibitory effects.
CD40L expression on activated lupus monocytes within anti-CD3-stimulated, mononuclear cell cultures was also enhanced compared to control-derived monocytes.
Anti-CD40 ligand antibody treatment prevents the development of lupus-like nephritis in a subset of New Zealand black x New Zealand white mice. Response correlates with the absence of an anti-antibody response.
Because hydroxychloroquine (HCQ) has been used frequently in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism.
Cell surface CD154 expression (pre- and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry.
Epigenetic deregulation of genes encoded on the X chromosome as reported for CD40L in lupus could explain the female predominance of autoimmune diseases.
Recent data from SLE patients and murine lupus models have demonstrated prolonged expression of CD40L on lupus T cells and its capacity to mediate excessive B cell activation.
Similar studies demonstrated that CD40LG demethylates in CD4(+) T cells from women with lupus, and that women but not men with lupus overexpress CD40LG on CD4(+) T cells, while both overexpress TNFSF7.
This activity was inhibited by anti-CD40L antibody, as well as anti-CD1d antibody, confirming a role for CD40L-CD40 and TCR-CD1d interactions in lupus iNKT-cell-mediated help.
This suggests that demethylation of genes on the inactive X may predispose women to lupus, and this hypothesis is supported by a report that CD40LG, an immune gene encoded on the X chromosome, demethylates and is overexpressed in T cells from women but not men with lupus.
Thus, these findings provide some of the first evidence to support a possible mechanistic link to explain how the overexpression of IL-15 observed in lupus patients may be involved in the prolonged expression of CD154 that has also been observed on lupus CD4 T cells.