cAMP-responsive element modulator α (CREMα) trans-represses the transmembrane glycoprotein CD8 and contributes to the generation of CD3+CD4-CD8- T cells in health and disease

J Biol Chem. 2013 Nov 1;288(44):31880-7. doi: 10.1074/jbc.M113.508655. Epub 2013 Sep 18.


T cell receptor-αβ(+) CD3(+)CD4(-)CD8(-) "double-negative" T cells are expanded in the peripheral blood of patients with systemic lupus erythematosus and autoimmune lymphoproliferative syndrome. In both disorders, double-negative T cells infiltrate tissues, induce immunoglobulin production, and secrete proinflammatory cytokines. Double-negative T cells derive from CD8(+) T cells through down-regulation of CD8 surface co-receptors. However, the molecular mechanisms orchestrating this process remain unclear. Here, we demonstrate that the transcription factor cAMP-responsive element modulator α (CREMα), which is expressed at increased levels in T cells from systemic lupus erythematosus patients, contributes to transcriptional silencing of CD8A and CD8B. We provide the first evidence that CREMα trans-represses a regulatory element 5' of the CD8B gene. Therefore, CREMα represents a promising candidate in the search for biomarkers and treatment options in diseases in which double-negative T cells contribute to the pathogenesis.

Keywords: Autoimmune Diseases; CD8; CREMα; Cell Differentiation; Cellular Immune Response; Double-negative T Cells; Gene Regulation; SLE; T Cell.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / biosynthesis*
  • CD8 Antigens / genetics
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cyclic AMP Response Element Modulator / genetics
  • Cyclic AMP Response Element Modulator / immunology
  • Cyclic AMP Response Element Modulator / metabolism*
  • Female
  • Gene Silencing*
  • Humans
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Repressor Proteins / metabolism*
  • Response Elements*
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology


  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • CD8beta antigen
  • CREM protein, human
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator