The role of TCR stimulation and TGF-beta in controlling the expression of CD94/NKG2A receptors on CD8 T cells

Eur J Immunol. 2005 Mar;35(3):766-75. doi: 10.1002/eji.200425735.


Following antigen recognition, murine CD8 T cells express CD94/NKG2A receptors. Our results show that this up-regulation occurs rapidly in vitro and is accompanied by an approximately 8-fold increase in CD94 and approximately 125-fold increase in NKG2A mRNA. In contrast, only a twofold increase in NKG2C mRNA is noted. The addition of TGF-beta, but not IL-10, IL-12 or IL-15, leads to a further increase in cell membrane expression of these receptors, as well as a approximately 6-fold increase in mRNA for both chains. TGF-beta also increases CD94/NKG2A expression on memory CD8 T cells that are re-exposed to antigen. The effect of TGF-beta on increasing CD94/NKG2A expression on both naive and memory CD8 T cells occurs only when there is a concurrent stimulation through the TCR. In contrast, TGF-beta does not increase expression of CD94/NKG2A on resting or activated NK cells. We also show by using purified CD8 T cells, that TGF-beta acts directly on these cells. These results implicate a role for both antigen and TGF-beta in increasing expression of inhibitory CD94/NKG2A receptors on CD8 T cells.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Flow Cytometry
  • Gene Expression
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation


  • Antigens, CD
  • Klrc1 protein, mouse
  • Klrc2 protein, mouse
  • Klrd1 protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Transforming Growth Factor beta