Abstract
CD40 ligand (CD40LG), encoded on the X chromosome, has been reported to be overexpressed on lupus T cells. Herein, we investigated the effect of DNA demethylation on T cell CD40LG expression and the production of IgG by autologous B cells in lupus. We found normal human T cells transfected with CD40LG induced autologous B cell activation and plasma cell differentiation. Both female lupus CD4+ T cells and demethylating agents treated CD4+ T cells overexpressed CD40LG mRNA. Further, lupus T cells from both genders or demethylated CD4+ T cells from healthy women overstimulated autologous B cells, and this could be reversed with anti-CD40LG Ab in only females. We demonstrated that female lupus CD4+ T cells and demethylated CD4+ T cells express high level of CD40LG and overstimulate B cells to produce IgG. This is due to DNA demethylation and thereby reactivation of the inactive X chromosome in female.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adolescent
-
Adult
-
Antibodies, Monoclonal / pharmacology
-
Antibody Formation / drug effects
-
Antibody Formation / immunology*
-
Antigens, CD / metabolism
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism
-
CD4-Positive T-Lymphocytes / drug effects
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism
-
CD40 Ligand / genetics*
-
CD40 Ligand / immunology
-
CD8-Positive T-Lymphocytes / drug effects
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
DNA Methylation / drug effects
-
Enzyme Inhibitors / pharmacology
-
Female
-
Gene Expression Regulation* / drug effects
-
Gene Expression Regulation* / immunology
-
Humans
-
Immunoglobulin G / immunology*
-
Lipopolysaccharides / pharmacology
-
Lupus Erythematosus, Systemic / immunology*
-
Lupus Erythematosus, Systemic / metabolism
-
Lymphocyte Activation / drug effects
-
Lymphocyte Activation / immunology
-
Male
-
Sex Characteristics
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / immunology
-
T-Lymphocytes / metabolism*
-
Transfection
-
Young Adult
Substances
-
Antibodies, Monoclonal
-
Antigens, CD
-
Enzyme Inhibitors
-
Immunoglobulin G
-
Lipopolysaccharides
-
CD40 Ligand