Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors

Arthritis Rheum. 2004 Jun;50(6):1850-60. doi: 10.1002/art.20255.


Objective: Generalized DNA hypomethylation contributes to altered T cell function and gene expression in systemic lupus erythematosus (SLE). Some of the overexpressed genes participate in the disease process, but the full repertoire of genes affected is unknown. Methylation-sensitive T cell genes were identified by treating T cells with the DNA methyltransferase inhibitor 5-azacytidine and comparing gene expression with oligonucleotide arrays. CD70, a costimulatory ligand for B cell CD27, was one gene that reproducibly increased. We then determined whether CD70 is overexpressed on T cells treated with other DNA methylation inhibitors and on SLE T cells, and determined its functional significance.

Methods: Oligonucleotide arrays, real-time reverse transcription-polymerase chain reaction, and flow cytometry were used to compare CD70 expression in T cells treated with 2 DNA methyltransferase inhibitors (5-azacytidine and procainamide) and 3 ERK pathway inhibitors known to decrease DNA methyltransferase expression (U0126, PD98059, and hydralazine). The consequences of CD70 overexpression were tested by coculture of autologous T and B cells with and without anti-CD70 and measuring IgG production by enzyme-linked immunosorbent assay. The results were compared with those of T cells from lupus patients.

Results: SLE T cells and T cells treated with DNA methylation inhibitors overexpressed CD70 and overstimulated B cell IgG production. The increase in IgG synthesis was abrogated by anti-CD70.

Conclusion: SLE T cells and T cells treated with DNA methyltransferase inhibitors and ERK pathway inhibitors overexpress CD70. This increased B cell costimulation and subsequent immunoglobulin overproduction may contribute to drug-induced and idiopathic lupus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics*
  • Azacitidine / pharmacology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / physiology
  • CD27 Ligand
  • DNA Methylation / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Humans
  • Immunoglobulin G / metabolism*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Platelet Aggregation Inhibitors / pharmacology
  • Procainamide / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*


  • Antigens, CD
  • CD27 Ligand
  • CD70 protein, human
  • Enzyme Inhibitors
  • Immunoglobulin G
  • Membrane Proteins
  • Platelet Aggregation Inhibitors
  • Procainamide
  • Azacitidine