Enhanced CD4+ T cell proliferation and Th2 cytokine production in DR6-deficient mice

Immunity. 2001 Jul;15(1):23-34. doi: 10.1016/s1074-7613(01)00162-5.


We have found that DR6, a member of the TNF receptor family, is highly expressed in resting T cells and downregulated in activated T cells. DR6-targeted mutant mice were generated and showed normal development. However, DR6(-/-) CD4(+) T cells hyperproliferated in response to TCR-mediated stimulation and protein antigen challenge. Activated DR6(-/-) CD4(+) T cells exhibited upregulated CD25 expression and enhanced proliferation in response to exogenous IL-2 stimulation. In addition, increased CD28 and reduced CTLA-4 expression were observed in these cells. Enhanced Th2 cytokine production by activated DR6(-/-) CD4(+) T cells was associated with the increased transcription factor NF-ATc in nuclei. DR6, therefore, functions as a regulatory receptor for mediating CD4(+) T cell activation and maintaining proper immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / analysis
  • CD28 Antigens / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Cytokines / biosynthesis*
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Immunoconjugates*
  • Lymphocyte Activation*
  • Mice
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Receptors, Interleukin-2 / analysis
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Transcription Factors / metabolism


  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Cytokines
  • DNA-Binding Proteins
  • Immunoconjugates
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Receptors, Interleukin-2
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf21 protein, mouse
  • Transcription Factors
  • Abatacept
  • DNA